rs1051295

Positions:

• chr20-49372368-A-G
• chr20-49372368-A-T

Variant summary

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

The NM_004975.4(KCNB1):​c.*615T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,314 control chromosomes in the GnomAD database, including 4,680 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 0.22 (4675 hom., cov: 32)
  • Exomes 𝑓: 0.21 (5 hom.)
• Consequence: KCNB1 NM_004975.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.475

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNB1	NM_004975.4	c.*615T>C		3_prime_UTR_variant	2/2	ENST00000371741.6	NP_004966.1
LOC105372649	XR_001754659.2	n.1201+40344A>G		intron_variant, non_coding_transcript_variant
KCNB1	XM_011528799.3	c.*615T>C		3_prime_UTR_variant	3/3		XP_011527101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNB1	ENST00000371741.6	c.*615T>C		3_prime_UTR_variant	2/2	1	NM_004975.4	ENSP00000360806	P1
	ENST00000637341.1	n.206+40344A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33775 AN: 152044 Hom.: 4657 Cov.: 32

Gnomad AFR AF: 0.0656

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.405

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.214

GnomAD4 exome AF: 0.211 AC: 32 AN: 152 Hom.: 5 Cov.: 0 AF XY: 0.228 AC XY: 21 AN XY: 92

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.293

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.222 AC: 33821 AN: 152162 Hom.: 4675 Cov.: 32 AF XY: 0.229 AC XY: 17030 AN XY: 74372

Gnomad4 AFR AF: 0.0659

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.404

Gnomad4 SAS AF: 0.250

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.219

Alfa AF: 0.251 Hom.: 7032

Bravo AF: 0.217

Asia WGS AF: 0.323 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1051295; hg19: chr20-47988905;