4-113064557-A-G

Variant names:

• chr4-113064557-A-G
• rs313975
• NM_001148.6:c.84+14745A>G

Variant summary

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

The ENST00000357077.9(ANK2):​c.84+14745A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,184 control chromosomes in the GnomAD database, including 58,648 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 0.87 (58648 hom., cov: 32)
• Consequence: ANK2 ENST00000357077.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.13
• Publications: 0 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000357077.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK2	NM_001148.6	MANE Select	c.84+14745A>G		intron	N/A	NP_001139.3
	ANK2	NM_001386142.1		c.22-109859A>G		intron	N/A	NP_001373071.1
	ANK2	NM_001386143.1		c.22-109859A>G		intron	N/A	NP_001373072.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK2	ENST00000357077.9	TSL:1 MANE Select	c.84+14745A>G		intron	N/A	ENSP00000349588.4
	ANK2	ENST00000394537.7	TSL:1	c.84+14745A>G		intron	N/A	ENSP00000378044.3
	ANK2	ENST00000506722.5	TSL:1	c.22-109859A>G		intron	N/A	ENSP00000421067.1

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132962 AN: 152066 Hom.: 58589 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.892

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.898

Gnomad FIN AF: 0.814

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.881

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

GnomAD4 genome AF: 0.874 AC: 133078 AN: 152184 Hom.: 58648 Cov.: 32 AF XY: 0.877 AC XY: 65252 AN XY: 74376

African (AFR) AF: 0.968 AC: 40221 AN: 41554

American (AMR) AF: 0.907 AC: 13848 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.892 AC: 3097 AN: 3472

East Asian (EAS) AF: 0.980 AC: 5074 AN: 5176

South Asian (SAS) AF: 0.897 AC: 4325 AN: 4824

European-Finnish (FIN) AF: 0.814 AC: 8612 AN: 10584

Middle Eastern (MID) AF: 0.891 AC: 262 AN: 294

European-Non Finnish (NFE) AF: 0.809 AC: 54996 AN: 67986

Other (OTH) AF: 0.882 AC: 1860 AN: 2108

Alfa AF: 0.783 Hom.: 2561

Bravo AF: 0.887

Asia WGS AF: 0.936 AC: 3253 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0020
DANN	Benign	0.59
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs313975; hg19: chr4-113985713;