10-90918981-AAAATAAATAAAT-AAAAT

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_014391.3(ANKRD1):c.346-17_346-10delATTTATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,269,304 control chromosomes in the GnomAD database, including 3,441 homozygotes. There is a variant allele frequency bias in the population database for this variant (GnomAd4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0059 ( 7 hom., cov: 0)

Exomes 𝑓: 0.020 ( 3434 hom. )

Consequence

ANKRD1
NM_014391.3 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:8

Conservation

PhyloP100: 3.19

Publications

3 publications found

Variant links:

Genes affected

ANKRD1 (HGNC:15819): (ankyrin repeat domain 1) The protein encoded by this gene is localized to the nucleus of endothelial cells and is induced by IL-1 and TNF-alpha stimulation. Studies in rat cardiomyocytes suggest that this gene functions as a transcription factor. Interactions between this protein and the sarcomeric proteins myopalladin and titin suggest that it may also be involved in the myofibrillar stretch-sensor system. [provided by RefSeq, Jul 2008]

ANKRD1 Gene-Disease associations (from GenCC):

familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ANKRD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP6

Variant 10-90918981-AAAATAAAT-A is Benign according to our data. Variant chr10-90918981-AAAATAAAT-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 45631.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD1	NM_014391.3 link	c.346-17_346-10delATTTATTT		intron_variant	Intron 3 of 8	ENST00000371697.4	NP_055206.2	Q15327A0A384NYH5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKRD1	ENST00000371697.4 link	c.346-17_346-10delATTTATTT		intron_variant	Intron 3 of 8	1	NM_014391.3	ENSP00000360762.3		Q15327

Frequencies

GnomAD3 genomes

AF:

0.00587

AC:

524

AN:

89238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00598

Gnomad AMI

AF:

0.00169

Gnomad AMR

AF:

0.00343

Gnomad ASJ

AF:

0.00316

Gnomad EAS

AF:

0.00588

Gnomad SAS

AF:

0.00566

Gnomad FIN

AF:

0.00638

Gnomad MID

AF:

0.00459

Gnomad NFE

AF:

0.00666

Gnomad OTH

AF:

0.00158

GnomAD2 exomes

AF:

0.127

AC:

10740

AN:

84372

AF XY:

0.119

show subpopulations

Gnomad AFR exome

AF:

0.410

Gnomad AMR exome

AF:

0.243

Gnomad ASJ exome

AF:

0.0573

Gnomad EAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.0706

Gnomad NFE exome

AF:

0.0675

Gnomad OTH exome

AF:

0.0980

GnomAD4 exome

AF:

0.0199

AC:

23458

AN:

1180070

Hom.:

3434

AF XY:

0.0206

AC XY:

12232

AN XY:

592942

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.134

AC:

2270

AN:

16922

American (AMR)

AF:

0.0713

AC:

2592

AN:

36358

Ashkenazi Jewish (ASJ)

AF:

0.0184

AC:

416

AN:

22630

East Asian (EAS)

AF:

0.0619

AC:

1746

AN:

28212

South Asian (SAS)

AF:

0.0519

AC:

3518

AN:

67806

European-Finnish (FIN)

AF:

0.0178

AC:

778

AN:

43668

Middle Eastern (MID)

AF:

0.0225

AC:

105

AN:

4662

European-Non Finnish (NFE)

AF:

0.0121

AC:

10989

AN:

911588

Other (OTH)

AF:

0.0216

AC:

1044

AN:

48224

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.340

Heterozygous variant carriers

1246

2492

3739

4985

6231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

392

784

1176

1568

1960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00588

AC:

525

AN:

89234

Hom.:

Cov.:

AF XY:

0.00604

AC XY:

258

AN XY:

42742

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00598

AC:

159

AN:

26608

American (AMR)

AF:

0.00343

AC:

AN:

8746

Ashkenazi Jewish (ASJ)

AF:

0.00316

AC:

AN:

2218

East Asian (EAS)

AF:

0.00619

AC:

AN:

3390

South Asian (SAS)

AF:

0.00567

AC:

AN:

2820

European-Finnish (FIN)

AF:

0.00638

AC:

AN:

4230

Middle Eastern (MID)

AF:

0.00505

AC:

AN:

198

European-Non Finnish (NFE)

AF:

0.00666

AC:

261

AN:

39168

Other (OTH)

AF:

0.00158

AC:

AN:

1266

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.304

Heterozygous variant carriers

105

158

210

263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:8

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Benign:3

Nov 11, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: ANKRD1 c.346-17_346-10delATTTATTT alters a non-conserved nucleotide located at a position not widely known to affect splicing. Several computational tools predict a significant impact on normal splicing: One predict the variant abolishes a canonical 3' acceptor site. Two predict the variant weakens a canonical 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.019 in 1269304 control chromosomes in the gnomAD database, including 3441 homozygotes. The observed variant frequency is approximately 755 fold of the estimated maximal expected allele frequency for a pathogenic variant in ANKRD1 causing Cardiomyopathy phenotype (2.5e-05). To our knowledge, no occurrence of c.346-17_346-10delATTTATTT in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 45631). Based on the evidence outlined above, the variant was classified as benign. -

Feb 20, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.346-17_346-10del variant in ANKRD1 has not been reported in the literature nor previously identified by our laboratory. This variant is located in a rep etitive region in intron 3 that contains several other common deletions and has been detected in 2/100 control chromosomes tested by our laboratory. Based on t he overall evidence for variants affecting this region and its frequency in cont rols this variant is likely benign. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Congenital total pulmonary venous return anomaly

Benign:3

Oct 11, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Oct 26, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dilated Cardiomyopathy, Dominant

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiomyopathy

Benign:1

Apr 08, 2013

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The variant is found in DCM panel(s). -

ANKRD1-related dilated cardiomyopathy

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over