NM_014391.3:c.346-19_346-14delTTATTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_014391.3(ANKRD1):c.346-19_346-14delTTATTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 301,188 control chromosomes in the GnomAD database, including 4,516 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 2543 hom., cov: 0)

Exomes 𝑓: 0.14 ( 1973 hom. )

Consequence

ANKRD1
NM_014391.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 3.19

Publications

2 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: Benign. The variant received -16 ACMG points.

BP6

Variant 10-90918985-TAAATAA-T is Benign according to our data. Variant chr10-90918985-TAAATAA-T is described in ClinVar as [Benign]. Clinvar id is 45632.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKRD1	NM_014391.3 link	c.346-19_346-14delTTATTT		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.346-19_346-14delTTATTT		intron_variant	Intron 3 of 8	1	NM_014391.3	ENSP00000360762.3		Q15327

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

17302

AN:

63404

Hom.:

2543

Cov.:

show subpopulations

Gnomad AFR

AF:

0.406

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.202

Gnomad EAS

AF:

0.392

Gnomad SAS

AF:

0.320

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.268

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.251

GnomAD2 exomes

AF:

0.0514

AC:

10913

AN:

212278

AF XY:

0.0495

show subpopulations

Gnomad AFR exome

AF:

0.183

Gnomad AMR exome

AF:

0.0434

Gnomad ASJ exome

AF:

0.0311

Gnomad EAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0458

Gnomad NFE exome

AF:

0.0297

Gnomad OTH exome

AF:

0.0367

GnomAD4 exome

AF:

0.143

AC:

34049

AN:

237782

Hom.:

1973

AF XY:

0.144

AC XY:

17244

AN XY:

119524

show subpopulations

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

African (AFR)

AF:

0.403

AC:

3315

AN:

8222

American (AMR)

AF:

0.350

AC:

1805

AN:

5150

Ashkenazi Jewish (ASJ)

AF:

0.143

AC:

657

AN:

4610

East Asian (EAS)

AF:

0.339

AC:

3226

AN:

9528

South Asian (SAS)

AF:

0.281

AC:

4162

AN:

14828

European-Finnish (FIN)

AF:

0.177

AC:

1475

AN:

8324

Middle Eastern (MID)

AF:

0.159

AC:

158

AN:

996

European-Non Finnish (NFE)

AF:

0.0993

AC:

17435

AN:

175552

Other (OTH)

AF:

0.172

AC:

1816

AN:

10572

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.372

Heterozygous variant carriers

1533

3066

4599

6132

7665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

788

1576

2364

3152

3940

<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:

0.273

AC:

17302

AN:

63406

Hom.:

2543

Cov.:

AF XY:

0.280

AC XY:

8573

AN XY:

30570

show subpopulations

African (AFR)

AF:

0.405

AC:

9598

AN:

23678

American (AMR)

AF:

0.301

AC:

2020

AN:

6722

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

272

AN:

1346

East Asian (EAS)

AF:

0.393

AC:

1050

AN:

2672

South Asian (SAS)

AF:

0.320

AC:

680

AN:

2124

European-Finnish (FIN)

AF:

0.227

AC:

617

AN:

2720

Middle Eastern (MID)

AF:

0.279

AC:

AN:

122

European-Non Finnish (NFE)

AF:

0.122

AC:

2779

AN:

22798

Other (OTH)

AF:

0.251

AC:

242

AN:

964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

444

888

1331

1775

2219

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.106

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 17, 2023

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

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 06, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

346-19_346-14del in intron 3 of ANKRD1: This variant is not expected to have cli nical significance because it has been identified in 6% (6/100) of control chrom osomes by our laboratory (LMM unpublished data). In addition, this variant lies within a highly variable region of the intron where multiple deletions of variou s sizes identified in the general population have been observed, suggesting that variation in this region is tolerated. -

Congenital total pulmonary venous return anomaly

Benign:1

May 11, 2016

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ANKRD1-related dilated cardiomyopathy

Benign:1

Feb 03, 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

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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