rs79793575

chr10-90919284-G-A

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.208-16C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,593,276 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (64 hom.)
• Consequence: ANKRD1 NM_014391.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.296

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=-0.8).
• BP6: Variant 10-90919284-G-A is Benign according to our data. Variant chr10-90919284-G-A is described in ClinVar as [Benign]. Clinvar id is 136401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-90919284-G-A is described in Lovd as [Benign]. Variant chr10-90919284-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD1	NM_014391.3	c.208-16C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000371697.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD1	ENST00000371697.4	c.208-16C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014391.3	P1

Frequencies

GnomAD3 genomes AF: 0.00224 AC: 340 AN: 151974 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000221

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00530 AC: 1253 AN: 236620 Hom.: 45 AF XY: 0.00489 AC XY: 629 AN XY: 128760

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000594

Gnomad ASJ exome AF: 0.00364

Gnomad EAS exome AF: 0.0656

Gnomad SAS exome AF: 0.00125

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000166

Gnomad OTH exome AF: 0.00170

GnomAD4 exome AF: 0.00158 AC: 2277 AN: 1441184 Hom.: 64 Cov.: 31 AF XY: 0.00164 AC XY: 1178 AN XY: 717298

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000182

Gnomad4 ASJ exome AF: 0.00290

Gnomad4 EAS exome AF: 0.0471

Gnomad4 SAS exome AF: 0.00168

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000625

Gnomad4 OTH exome AF: 0.00220

GnomAD4 genome AF: 0.00223 AC: 339 AN: 152092 Hom.: 10 Cov.: 32 AF XY: 0.00266 AC XY: 198 AN XY: 74346

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0571

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.000710 Hom.: 0

Bravo AF: 0.00286

Asia WGS AF: 0.0160 AC: 55 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 15, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Congenital total pulmonary venous return anomaly Benign:2

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jul 31, 2017

Variant summary: The ANKRD1 c.208-16C>T variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 547/108416 control chromosomes (19 homozygotes), predominantly observed in the East Asian subpopulation at a frequency of 0.067417 (509/7550; 18 homozygotes). This frequency is about 1961 times the estimated maximal expected allele frequency of a pathogenic ANKRD1 variant (0.0000344), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, one clinical diagnostic laboratory has classified this variant as benign. It has also been published as a polymorphism in the literature (Arimura_2009). Taken together, this variant is classified as benign. -

ANKRD1-related dilated cardiomyopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.23
Dann	Benign	0.79

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: rs79793575; hg19: chr10-92679041; COSMIC: COSV63311228; COSMIC: COSV63311228;