rs610412

chr20-49461665-A-C

Variant summary

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

The NM_004975.4(KCNB1):c.567+20249T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,036 control chromosomes in the GnomAD database, including 9,434 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 0.35 (9434 hom., cov: 32)
• Consequence: KCNB1 NM_004975.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.645

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.386 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNB1	NM_004975.4	c.567+20249T>G		intron_variant		ENST00000371741.6
KCNB1	XM_011528799.3	c.567+20249T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNB1	ENST00000371741.6	c.567+20249T>G		intron_variant		1	NM_004975.4	P1
KCNB1	ENST00000635465.1	c.567+20249T>G		intron_variant		1		P1
KCNB1	ENST00000635878.1	c.96+20249T>G		intron_variant		5
KCNB1	ENST00000636950.1	n.88-10248T>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52632 AN: 151918 Hom.: 9436 Cov.: 32

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.346 AC: 52637 AN: 152036 Hom.: 9434 Cov.: 32 AF XY: 0.344 AC XY: 25551 AN XY: 74322

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.363

Gnomad4 NFE AF: 0.390

Gnomad4 OTH AF: 0.378

Alfa AF: 0.374 Hom.: 2612

Bravo AF: 0.344

Asia WGS AF: 0.224 AC: 777 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	17
Dann	Benign	0.77

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: rs610412; hg19: chr20-48078202;