chr4-112997547-T-C

Variant names:

• chr4-112997547-T-C
• rs1354679
• ENST00000506722.5:c.21+93033T>C

Variant summary

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

The NM_001386142.1(ANK2):​c.21+93033T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,896 control chromosomes in the GnomAD database, including 13,496 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 0.39 (13496 hom., cov: 32)
• Consequence: ANK2 NM_001386142.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK2	NM_001386142.1	c.21+93033T>C		intron_variant	Intron 2 of 44		NP_001373071.1
ANK2	NM_001386143.1	c.21+93033T>C		intron_variant	Intron 2 of 47		NP_001373072.1
ANK2	NM_001386186.2	c.73-176869T>C		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+93033T>C		intron_variant	Intron 2 of 46	1		ENSP00000421067.1
ANK2	ENST00000672209.1	c.21+93033T>C		intron_variant	Intron 2 of 47			ENSP00000499982.1
ANK2	ENST00000673298.1	c.21+93033T>C		intron_variant	Intron 2 of 46			ENSP00000500245.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59731 AN: 151778 Hom.: 13456 Cov.: 32

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.394 AC: 59835 AN: 151896 Hom.: 13496 Cov.: 32 AF XY: 0.398 AC XY: 29563 AN XY: 74248

Gnomad4 AFR AF: 0.615

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.386

Alfa AF: 0.289 Hom.: 4226

Bravo AF: 0.405

Asia WGS AF: 0.529 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1354679; hg19: chr4-113918703;