rs1467847

Variant names:

• chr21-34342245-G-C
• rs1467847
• ENST00000715813.1:c.-2472-17661G>C

Your query was ambiguous. Multiple possible variants found:

• chr21-34342245-G-C
• chr21-34342245-G-T

Variant summary

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

The ENST00000715813.1(KCNE2):​c.-2472-17661G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 151,906 control chromosomes in the GnomAD database, including 20,509 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 0.50 (20509 hom., cov: 31)
• Consequence: KCNE2 ENST00000715813.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406
• Publications: 7 publications found

Genes affected

KCNE2 (HGNC:6242): (potassium voltage-gated channel subfamily E regulatory subunit 2) Voltage-gated potassium (Kv) channels represent the most complex class of voltage-gated ion channels from both functional and structural standpoints. Their diverse functions include regulating neurotransmitter release, heart rate, insulin secretion, neuronal excitability, epithelial electrolyte transport, smooth muscle contraction, and cell volume. This gene encodes a member of the potassium channel, voltage-gated, isk-related subfamily. This member is a small integral membrane subunit that assembles with the KCNH2 gene product, a pore-forming protein, to alter its function. This gene is expressed in heart and muscle and the gene mutations are associated with cardiac arrhythmia. [provided by RefSeq, Jul 2008]

MRPS6 (HGNC:14051): (mitochondrial ribosomal protein S6) Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that belongs to the ribosomal protein S6P family. Pseudogenes corresponding to this gene are found on chromosomes 1p and 12q. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNE2	ENST00000715813.1	c.-2472-17661G>C		intron_variant	Intron 3 of 5			ENSP00000520524.1
MRPS6	ENST00000362077.5	n.*156-17661G>C		intron_variant	Intron 5 of 6	3		ENSP00000520522.1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76271 AN: 151788 Hom.: 20509 Cov.: 31

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.497

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.644

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.502 AC: 76282 AN: 151906 Hom.: 20509 Cov.: 31 AF XY: 0.509 AC XY: 37796 AN XY: 74248

African (AFR) AF: 0.307 AC: 12701 AN: 41414

American (AMR) AF: 0.634 AC: 9687 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1632 AN: 3466

East Asian (EAS) AF: 0.456 AC: 2349 AN: 5148

South Asian (SAS) AF: 0.531 AC: 2559 AN: 4818

European-Finnish (FIN) AF: 0.644 AC: 6789 AN: 10544

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.573 AC: 38909 AN: 67932

Other (OTH) AF: 0.498 AC: 1048 AN: 2104

Alfa AF: 0.445 Hom.: 1504

Bravo AF: 0.492

Asia WGS AF: 0.456 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.71
PhyloP100		0.41

Splicing

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

Other links and lift over

dbSNP: rs1467847; hg19: chr21-35714544;