10-90915892-GAA-GA

Position:

• chr10-90915892-GAA-GA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The ENST00000371697.4(ANKRD1):​c.652-13del 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 0.157 in 1,611,048 control chromosomes in the GnomAD database, including 20,419 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2332 hom., cov: 25)
  • Exomes 𝑓: 0.16 (18087 hom.)
• Consequence: ANKRD1 ENST00000371697.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 2.87

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 -16 ACMG points.

• BP6: Variant 10-90915892-GA-G is Benign according to our data. Variant chr10-90915892-GA-G is described in ClinVar as [Likely_benign]. Clinvar id is 201661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-90915892-GA-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANKRD1	NM_014391.3	c.652-13del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000371697.4	NP_055206.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKRD1	ENST00000371697.4	c.652-13del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_014391.3	ENSP00000360762	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26111 AN: 151198 Hom.: 2326 Cov.: 25

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.0474

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.133

GnomAD3 exomes AF: 0.150 AC: 37486 AN: 249262 Hom.: 2910 AF XY: 0.151 AC XY: 20297 AN XY: 134794

Gnomad AFR exome AF: 0.230

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.101

Gnomad EAS exome AF: 0.153

Gnomad SAS exome AF: 0.135

Gnomad FIN exome AF: 0.150

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.144

GnomAD4 exome AF: 0.155 AC: 226340 AN: 1459732 Hom.: 18087 Cov.: 30 AF XY: 0.155 AC XY: 112313 AN XY: 726162

Gnomad4 AFR exome AF: 0.230

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.151

Gnomad4 NFE exome AF: 0.157

Gnomad4 OTH exome AF: 0.150

GnomAD4 genome AF: 0.173 AC: 26145 AN: 151316 Hom.: 2332 Cov.: 25 AF XY: 0.171 AC XY: 12627 AN XY: 73900

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.134

Alfa AF: 0.166 Hom.: 383

Bravo AF: 0.172

Asia WGS AF: 0.159 AC: 554 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2018	- -
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.652-13delT variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts a benign outcome for this variant. 3/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 18376/112060 control chromosomes (1459 homozygotes) from ExAC at a frequency of 0.1639836, which is approximately 4770 times the estimated maximal expected allele frequency of a pathogenic ANKRD1 variant (0.0000344), thus it is a common benign polymorphism. This variant has also been reported as a polymorphism in the literature (Arimura_2009). In addition, multiple clinical diagnostic laboratories/reputable databases have classified this variant as benign/likely benign. Taken together, this variant is classified as benign. -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Dilated Cardiomyopathy, Dominant Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

ANKRD1-related dilated cardiomyopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Hypertrophic cardiomyopathy 2 Benign:1

Benign, no assertion criteria provided

clinical testing

Institute of Human Genetics, University of Wuerzburg

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs3839929; hg19: chr10-92675649;