chr10-90912291-TAAAAAAAAA-T

Position:

• chr10-90912291-TAAAAAAAAA-T

Variant summary

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

The NM_014391.3(ANKRD1):​c.*566_*574del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0684 in 234 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.021 (30 hom., cov: 0)
  • Exomes 𝑓: 0.068 (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: 1.63

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 amr. gnomad4_exome allele frequency = 0.0684 (16/234) while in subpopulation AMR AF= 0.1 (5/50). AF 95% confidence interval is 0.0394. There are 0 homozygotes in gnomad4_exome. There are 7 alleles in male gnomad4_exome subpopulation. 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.*566_*574del		3_prime_UTR_variant	9/9	ENST00000371697.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANKRD1	ENST00000371697.4	c.*566_*574del		3_prime_UTR_variant	9/9	1	NM_014391.3	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1460 AN: 70388 Hom.: 30 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00885

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.0220

Gnomad ASJ AF: 0.0296

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00617

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0313

Gnomad NFE AF: 0.0259

Gnomad OTH AF: 0.0203

GnomAD4 exome AF: 0.0684 AC: 16 AN: 234 Hom.: 0 AF XY: 0.0660 AC XY: 7 AN XY: 106

Gnomad4 AMR exome AF: 0.100

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0714

Gnomad4 NFE exome AF: 0.0625

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0207 AC: 1460 AN: 70402 Hom.: 30 Cov.: 0 AF XY: 0.0201 AC XY: 635 AN XY: 31630

Gnomad4 AFR AF: 0.00889

Gnomad4 AMR AF: 0.0220

Gnomad4 ASJ AF: 0.0296

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00618

Gnomad4 FIN AF: 0.0448

Gnomad4 NFE AF: 0.0259

Gnomad4 OTH AF: 0.0204

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;