4-113067963-C-T

Variant names:

• chr4-113067963-C-T
• rs689117
• NM_001148.6:c.84+18151C>T

Variant summary

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

The NM_001148.6(ANK2):​c.84+18151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.806 in 152,190 control chromosomes in the GnomAD database, including 49,756 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 0.81 (49756 hom., cov: 32)
• Consequence: ANK2 NM_001148.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001148.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK2	NM_001148.6	MANE Select	c.84+18151C>T		intron	N/A	NP_001139.3
	ANK2	NM_001386142.1		c.22-106453C>T		intron	N/A	NP_001373071.1
	ANK2	NM_001386143.1		c.22-106453C>T		intron	N/A	NP_001373072.1	A0A5F9ZGZ1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ANK2	ENST00000357077.9	TSL:1 MANE Select	c.84+18151C>T		intron	N/A	ENSP00000349588.4	Q01484-4
	ANK2	ENST00000394537.7	TSL:1	c.84+18151C>T		intron	N/A	ENSP00000378044.3	Q01484-2
	ANK2	ENST00000506722.5	TSL:1	c.22-106453C>T		intron	N/A	ENSP00000421067.1	Q01484-5

Frequencies

GnomAD3 genomes AF: 0.805 AC: 122494 AN: 152072 Hom.: 49709 Cov.: 32

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.852

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.818

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.817

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

GnomAD4 genome AF: 0.806 AC: 122598 AN: 152190 Hom.: 49756 Cov.: 32 AF XY: 0.806 AC XY: 59940 AN XY: 74388

African (AFR) AF: 0.891 AC: 37031 AN: 41560

American (AMR) AF: 0.794 AC: 12127 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.852 AC: 2955 AN: 3470

East Asian (EAS) AF: 0.871 AC: 4509 AN: 5174

South Asian (SAS) AF: 0.799 AC: 3848 AN: 4818

European-Finnish (FIN) AF: 0.743 AC: 7855 AN: 10578

Middle Eastern (MID) AF: 0.822 AC: 240 AN: 292

European-Non Finnish (NFE) AF: 0.760 AC: 51686 AN: 67994

Other (OTH) AF: 0.815 AC: 1725 AN: 2116

Alfa AF: 0.779 Hom.: 56118

Bravo AF: 0.813

Asia WGS AF: 0.811 AC: 2818 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.86
DANN	Benign	0.42
PhyloP100		-0.38
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: rs689117; hg19: chr4-113989119;