rs137914723

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PP3BP6_Very_StrongBA1

The NM_014391.3(ANKRD1):c.348G>A(p.Thr116Thr) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00379 in 1,564,118 control chromosomes in the GnomAD database, including 356 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0077 ( 40 hom., cov: 29)

Exomes 𝑓: 0.0034 ( 316 hom. )

Consequence

ANKRD1
NM_014391.3 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.186

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
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
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 -15 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

BP6

Variant 10-90918970-C-T is Benign according to our data. Variant chr10-90918970-C-T is described in ClinVar as Benign. ClinVar VariationId is 45633.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.059 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014391.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANKRD1	NM_014391.3	MANE Select	c.348G>A	p.Thr116Thr	splice_region synonymous	Exon 4 of 9	NP_055206.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANKRD1	ENST00000371697.4	TSL:1 MANE Select	c.348G>A	p.Thr116Thr	splice_region synonymous	Exon 4 of 9	ENSP00000360762.3	Q15327
ANKRD1	ENST00000869698.1		c.348G>A	p.Thr116Thr	splice_region synonymous	Exon 4 of 8	ENSP00000539757.1
ANKRD1	ENST00000945870.1		c.348G>A	p.Thr116Thr	splice_region synonymous	Exon 4 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes

AF:

0.00771

AC:

1026

AN:

133122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0622

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0124

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000185

Gnomad OTH

AF:

0.0165

GnomAD2 exomes

AF:

0.0146

AC:

3526

AN:

240686

AF XY:

0.0108

show subpopulations

Gnomad AFR exome

AF:

0.00143

Gnomad AMR exome

AF:

0.0979

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.000112

Gnomad NFE exome

AF:

0.000145

Gnomad OTH exome

AF:

0.00973

GnomAD4 exome

AF:

0.00342

AC:

4896

AN:

1430932

Hom.:

316

Cov.:

AF XY:

0.00286

AC XY:

2039

AN XY:

713034

show subpopulations

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

African (AFR)

AF:

0.00133

AC:

AN:

30804

American (AMR)

AF:

0.0939

AC:

4050

AN:

43120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25804

East Asian (EAS)

AF:

0.0141

AC:

531

AN:

37644

South Asian (SAS)

AF:

0.000293

AC:

AN:

85340

European-Finnish (FIN)

AF:

0.0000592

AC:

AN:

50710

Middle Eastern (MID)

AF:

0.000177

AC:

AN:

5644

European-Non Finnish (NFE)

AF:

0.0000576

AC:

AN:

1092984

Other (OTH)

AF:

0.00309

AC:

182

AN:

58882

⚠️ 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: 0.396

Heterozygous variant carriers

164

329

493

658

822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

228

304

380

<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:

0.00775

AC:

1032

AN:

133186

Hom.:

Cov.:

AF XY:

0.00851

AC XY:

551

AN XY:

64736

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

30328

American (AMR)

AF:

0.0625

AC:

862

AN:

13800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3388

East Asian (EAS)

AF:

0.0127

AC:

AN:

4504

South Asian (SAS)

AF:

0.00

AC:

AN:

4150

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9162

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.000185

AC:

AN:

64786

Other (OTH)

AF:

0.0164

AC:

AN:

1890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00295

Hom.:

Bravo

AF:

0.0129

Asia WGS

AF:

0.00665

AC:

AN:

3474

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (3)

ANKRD1-related dilated cardiomyopathy (1)

Cardiomyopathy (1)

Cardiovascular phenotype (1)

Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

-0.19

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.56

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.56

Position offset: -2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over