rs1395114

Variant names:

• chr4-113032425-C-T
• rs1395114
• ENST00000506722.5:c.21+127911C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000506722.5(ANK2):​c.21+127911C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 151,876 control chromosomes in the GnomAD database, including 3,404 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 0.20 (3404 hom., cov: 32)
• Consequence: ANK2 ENST00000506722.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 5 publications found

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)

ENSG00000249373 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK2	NM_001386142.1	c.21+127911C>T		intron_variant	Intron 2 of 44		NP_001373071.1
ANK2	NM_001386143.1	c.21+127911C>T		intron_variant	Intron 2 of 47		NP_001373072.1
ANK2	NM_001386186.2	c.73-141991C>T		intron_variant	Intron 1 of 46		NP_001373115.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000506722.5	c.21+127911C>T		intron_variant	Intron 2 of 46	1		ENSP00000421067.1
ANK2	ENST00000672209.1	c.21+127911C>T		intron_variant	Intron 2 of 47			ENSP00000499982.1
ANK2	ENST00000673298.1	c.21+127911C>T		intron_variant	Intron 2 of 46			ENSP00000500245.1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29636 AN: 151758 Hom.: 3393 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.195 AC: 29649 AN: 151876 Hom.: 3404 Cov.: 32 AF XY: 0.204 AC XY: 15122 AN XY: 74238

African (AFR) AF: 0.119 AC: 4933 AN: 41480

American (AMR) AF: 0.286 AC: 4348 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 385 AN: 3468

East Asian (EAS) AF: 0.433 AC: 2217 AN: 5124

South Asian (SAS) AF: 0.236 AC: 1137 AN: 4814

European-Finnish (FIN) AF: 0.287 AC: 3034 AN: 10568

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13078 AN: 67896

Other (OTH) AF: 0.186 AC: 392 AN: 2106

Alfa AF: 0.192 Hom.: 5166

Bravo AF: 0.193

Asia WGS AF: 0.294 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.34
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1395114; hg19: chr4-113953581;