chr20-49410025-T-G

Position:

• chr20-49410025-T-G

Variant summary

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

The NM_004975.4(KCNB1):​c.568-35033A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 151,918 control chromosomes in the GnomAD database, including 14,085 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 0.43 (14085 hom., cov: 31)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227

Genes affected

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNB1	NM_004975.4	c.568-35033A>C		intron_variant		ENST00000371741.6	NP_004966.1
LOC105372649	XR_001754659.2	n.1202-16627T>G		intron_variant, non_coding_transcript_variant
KCNB1	XM_011528799.3	c.568-35033A>C		intron_variant			XP_011527101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNB1	ENST00000371741.6	c.568-35033A>C		intron_variant		1	NM_004975.4	ENSP00000360806	P1
KCNB1	ENST00000635465.1	c.568-35033A>C		intron_variant		1		ENSP00000489193	P1
	ENST00000637341.1	n.207-13067T>G		intron_variant, non_coding_transcript_variant		5
KCNB1	ENST00000635878.1	c.96+71889A>C		intron_variant		5		ENSP00000489908

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65460 AN: 151800 Hom.: 14067 Cov.: 31

Gnomad AFR AF: 0.415

Gnomad AMI AF: 0.571

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.431 AC: 65529 AN: 151918 Hom.: 14085 Cov.: 31 AF XY: 0.430 AC XY: 31936 AN XY: 74232

Gnomad4 AFR AF: 0.416

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.395

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.414

Alfa AF: 0.442 Hom.: 6989

Bravo AF: 0.425

Asia WGS AF: 0.445 AC: 1549 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.7
DANN	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs6090975; hg19: chr20-48026562;