Variant 10-90912807-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014391.3(ANKRD1):c.*59A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 1,458,726 control chromosomes in the GnomAD database, including 161,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12678 hom., cov: 32)

Exomes 𝑓: 0.47 ( 149293 hom. )

Consequence

ANKRD1
NM_014391.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.638

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 10-90912807-T-C is Benign according to our data. Variant chr10-90912807-T-C is described in ClinVar as [Benign]. Clinvar id is 301603.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-90912807-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD1	NM_014391.3 linkuse as main transcript	c.*59A>G		3_prime_UTR_variant	9/9	ENST00000371697.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD1	ENST00000371697.4 linkuse as main transcript	c.*59A>G		3_prime_UTR_variant	9/9	1	NM_014391.3	P1

Frequencies

GnomAD3 genomes

AF:

0.393

AC:

59725

AN:

152034

Hom.:

12682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.537

Gnomad AMR

AF:

0.463

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.364

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.454

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.475

Gnomad OTH

AF:

0.414

GnomAD4 exome

AF:

0.473

AC:

617617

AN:

1306574

Hom.:

149293

Cov.:

AF XY:

0.471

AC XY:

309912

AN XY:

658412

show subpopulations

Gnomad4 AFR exome

AF:

0.195

Gnomad4 AMR exome

AF:

0.490

Gnomad4 ASJ exome

AF:

0.474

Gnomad4 EAS exome

AF:

0.360

Gnomad4 SAS exome

AF:

0.402

Gnomad4 FIN exome

AF:

0.461

Gnomad4 NFE exome

AF:

0.493

Gnomad4 OTH exome

AF:

0.457

GnomAD4 genome

AF:

0.393

AC:

59732

AN:

152152

Hom.:

12678

Cov.:

AF XY:

0.393

AC XY:

29246

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.463

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.363

Gnomad4 SAS

AF:

0.409

Gnomad4 FIN

AF:

0.454

Gnomad4 NFE

AF:

0.475

Gnomad4 OTH

AF:

0.414

Alfa

AF:

0.462

Hom.:

18113

Bravo

AF:

0.385

Asia WGS

AF:

0.371

AC:

1294

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	- -

Primary dilated cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.5

DANN

Benign

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over