rs237484

chr20-49358478-A-Gchr20-49358478-A-T

Variant summary

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

The ENST00000637341.1(ENSG00000290421):n.206+26454A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 151,882 control chromosomes in the GnomAD database, including 26,006 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 0.58 (26006 hom., cov: 30)
• Consequence: ENST00000637341.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.915

Genes affected

(HGNC:):

KCNB1 (HGNC:6231): (potassium voltage-gated channel subfamily B member 1) 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. Four sequence-related potassium channel genes - shaker, shaw, shab, and shal - have been identified in Drosophila, and each has been shown to have human homolog(s). This gene encodes a member of the potassium channel, voltage-gated, shab-related subfamily. This member is a delayed rectifier potassium channel and its activity is modulated by some other family members. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC105372649	XR_001754659.2	n.1201+26454A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000637341.1	n.206+26454A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.582 AC: 88263 AN: 151764 Hom.: 25951 Cov.: 30

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.621

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.582 AC: 88369 AN: 151882 Hom.: 26006 Cov.: 30 AF XY: 0.584 AC XY: 43368 AN XY: 74204

Gnomad4 AFR AF: 0.658

Gnomad4 AMR AF: 0.584

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.596

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.539

Alfa AF: 0.551 Hom.: 12029

Bravo AF: 0.585

Asia WGS AF: 0.606 AC: 2108 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.70
Dann	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs237484; hg19: chr20-47975015;