chr4-113036858-C-T

Position:

• chr4-113036858-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000506722.5(ANK2):​c.21+132344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 151,654 control chromosomes in the GnomAD database, including 51,926 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.82 (51926 hom., cov: 30)
• Consequence: ANK2 ENST00000506722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.523

Genes affected

ANK2 (HGNC:493): (ankyrin 2) This gene encodes a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. The protein encoded by this gene is required for targeting and stability of Na/Ca exchanger 1 in cardiomyocytes. Mutations in this gene cause long QT syndrome 4 and cardiac arrhythmia syndrome. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2011]

ANK2-AS1 (HGNC:40076): (ANK2 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ANK2-AS1	XR_007058232.1	n.273-765G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANK2-AS1	ENST00000508959.1	n.126-2064G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.822 AC: 124582 AN: 151536 Hom.: 51901 Cov.: 30

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.855

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.883

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.836

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.822 AC: 124653 AN: 151654 Hom.: 51926 Cov.: 30 AF XY: 0.826 AC XY: 61203 AN XY: 74080

Gnomad4 AFR AF: 0.671

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.970

Gnomad4 SAS AF: 0.862

Gnomad4 FIN AF: 0.883

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.838

Alfa AF: 0.840 Hom.: 8523

Bravo AF: 0.819

Asia WGS AF: 0.901 AC: 3133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.29
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10155204; hg19: chr4-113958014;