Variant 10-90912500-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014391.3(ANKRD1):c.*366G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0123 in 263,790 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 11 hom., cov: 31)

Exomes 𝑓: 0.014 ( 21 hom. )

Consequence

ANKRD1
NM_014391.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.20

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:

Genome browser will be placed here

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 10-90912500-C-T is Benign according to our data. Variant chr10-90912500-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 880084.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0107 (1631/152096) while in subpopulation NFE AF= 0.0183 (1246/68002). AF 95% confidence interval is 0.0175. There are 11 homozygotes in gnomad4. There are 713 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD1	NM_014391.3 linkuse as main transcript	c.*366G>A		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.*366G>A		3_prime_UTR_variant	9/9	1	NM_014391.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1632

AN:

151978

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00329

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00583

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00785

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0183

Gnomad OTH

AF:

0.00766

GnomAD4 exome

AF:

0.0144

AC:

1609

AN:

111694

Hom.:

Cov.:

AF XY:

0.0132

AC XY:

783

AN XY:

59310

show subpopulations

Gnomad4 AFR exome

AF:

0.00290

Gnomad4 AMR exome

AF:

0.00376

Gnomad4 ASJ exome

AF:

0.00823

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00471

Gnomad4 FIN exome

AF:

0.0141

Gnomad4 NFE exome

AF:

0.0199

Gnomad4 OTH exome

AF:

0.0144

GnomAD4 genome

AF:

0.0107

AC:

1631

AN:

152096

Hom.:

Cov.:

AF XY:

0.00959

AC XY:

713

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.00328

Gnomad4 AMR

AF:

0.00582

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00785

Gnomad4 NFE

AF:

0.0183

Gnomad4 OTH

AF:

0.00758

Alfa

AF:

0.0142

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Primary dilated cardiomyopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.077

DANN

Benign

0.30

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