rs3939

chr10-90912807-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.638

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]

ACMG classification

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	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	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.: 32

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.: 18 AF XY: 0.471 AC XY: 309912 AN XY: 658412

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.: 32 AF XY: 0.393 AC XY: 29246 AN XY: 74384

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

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

Other links and lift over

dbSNP: rs3939; hg19: chr10-92672564; COSMIC: COSV65467427; COSMIC: COSV65467427;