chr10-90920228-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014391.3(ANKRD1):c.148G>C(p.Ala50Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000656 in 1,614,092 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A50S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0036 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00035 ( 5 hom. )

Consequence

ANKRD1
NM_014391.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.510

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004582107).

BP6

Variant 10-90920228-C-G is Benign according to our data. Variant chr10-90920228-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 45625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 541 AD gene.

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.148G>C	p.Ala50Pro	missense	Exon 2 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.148G>C	p.Ala50Pro	missense	Exon 2 of 9	ENSP00000360762.3	Q15327
ANKRD1	ENST00000869698.1		c.148G>C	p.Ala50Pro	missense	Exon 2 of 8	ENSP00000539757.1
ANKRD1	ENST00000945870.1		c.148G>C	p.Ala50Pro	missense	Exon 2 of 8	ENSP00000615929.1

Frequencies

GnomAD3 genomes

AF:

0.00354

AC:

538

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.000891

AC:

224

AN:

251310

AF XY:

0.000722

show subpopulations

Gnomad AFR exome

AF:

0.0123

Gnomad AMR exome

AF:

0.000520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000354

AC:

518

AN:

1461844

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

232

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0124

AC:

416

AN:

33478

American (AMR)

AF:

0.000693

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000870

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1111992

Other (OTH)

AF:

0.000844

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

127

159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00355

AC:

541

AN:

152248

Hom.:

Cov.:

AF XY:

0.00349

AC XY:

260

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0121

AC:

502

AN:

41532

American (AMR)

AF:

0.00203

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68010

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

118

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:

0.000290

Hom.:

Bravo

AF:

0.00383

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00110

AC:

133

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Benign/Likely 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)

Congenital total pulmonary venous return anomaly (1)

Long QT syndrome (1)

Primary dilated cardiomyopathy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.077

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0046

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.6

PhyloP100

0.51

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.26

REVEL

Benign

0.056

Sift

Benign

0.31

Sift4G

Benign

0.27

Polyphen

0.031

Vest4

0.27

MVP

0.76

MPC

0.22

ClinPred

0.0016

GERP RS

0.18

Varity_R

0.15

gMVP

0.40

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over