ENST00000440403.2:n.1287G>A

Variant names:

• chr21-34354455-C-T
• rs2834465
• ENST00000440403.2:n.1287G>A

Variant summary

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

The ENST00000440403.2(ENSG00000225555):​n.1287G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,144 control chromosomes in the GnomAD database, including 4,098 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 0.21 (4098 hom., cov: 32)
• Consequence: ENSG00000225555 ENST00000440403.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08
• Publications: 2 publications found

Genes affected

ENSG00000225555 (HGNC:):

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=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105372791	NR_188571.1	n.1285G>A		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000225555	ENST00000440403.2	n.1287G>A		non_coding_transcript_exon_variant	Exon 3 of 3	3
KCNE2	ENST00000715813.1	c.-2472-5451C>T		intron_variant	Intron 3 of 5			ENSP00000520524.1
MRPS6	ENST00000362077.5	n.*156-5451C>T		intron_variant	Intron 5 of 6	3		ENSP00000520522.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31491 AN: 152026 Hom.: 4091 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.194

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

GnomAD4 genome AF: 0.207 AC: 31543 AN: 152144 Hom.: 4098 Cov.: 32 AF XY: 0.206 AC XY: 15346 AN XY: 74382

African (AFR) AF: 0.361 AC: 14978 AN: 41476

American (AMR) AF: 0.169 AC: 2577 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 663 AN: 3468

East Asian (EAS) AF: 0.203 AC: 1052 AN: 5180

South Asian (SAS) AF: 0.241 AC: 1161 AN: 4826

European-Finnish (FIN) AF: 0.114 AC: 1204 AN: 10584

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9324 AN: 68002

Other (OTH) AF: 0.196 AC: 415 AN: 2112

Alfa AF: 0.161 Hom.: 2990

Bravo AF: 0.214

Asia WGS AF: 0.216 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.1
DANN	Benign	0.86
PhyloP100		1.1

Splicing

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

Other links and lift over

dbSNP: rs2834465; hg19: chr21-35726754;