10-90912291-T-TAAAA

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_014391.3(ANKRD1):c.*574_*575insTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1800 hom., cov: 0)
  • Exomes 𝑓: 0.052 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ANKRD1 NM_014391.3 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.12

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 Likely_benign. Variant got -1 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0517 (12/232) while in subpopulation NFE AF= 0.0633 (10/158). AF 95% confidence interval is 0.0343. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANKRD1	NM_014391.3	c.*574_*575insTTTT		3_prime_UTR_variant	9/9	ENST00000371697.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD1	ENST00000371697.4	c.*574_*575insTTTT		3_prime_UTR_variant	9/9	1	NM_014391.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 10839 AN: 69974 Hom.: 1800 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.0517 AC: 12 AN: 232 Hom.: 0 Cov.: 0 AF XY: 0.0660 AC XY: 7 AN XY: 106

Gnomad4 AMR exome AF: 0.0200

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0633

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.155 AC: 10841 AN: 69990 Hom.: 1800 Cov.: 0 AF XY: 0.147 AC XY: 4628 AN XY: 31428

Gnomad4 AFR AF: 0.0510

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.102

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.0841

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.155

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Dilated Cardiomyopathy, Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71025330; hg19: chr10-92672048;