8-72567890-G-T

Variant names:

• chr8-72567890-G-T
• rs34259157
• NM_004770.3:c.156G>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004770.3(KCNB2):​c.156G>T​(p.Thr52Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00405 in 1,613,992 control chromosomes in the GnomAD database, including 207 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (100 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (107 hom.)
• Consequence: KCNB2 NM_004770.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.416

Genes affected

KCNB2 (HGNC:6232): (potassium voltage-gated channel subfamily B member 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. 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. The gene is expressed in gastrointestinal smooth muscle cells. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 8-72567890-G-T is Benign according to our data. Variant chr8-72567890-G-T is described in ClinVar as [Benign]. Clinvar id is 770572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.416 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0708 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNB2	NM_004770.3	c.156G>T	p.Thr52Thr	synonymous_variant	Exon 2 of 3	ENST00000523207.2	NP_004761.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNB2	ENST00000523207.2	c.156G>T	p.Thr52Thr	synonymous_variant	Exon 2 of 3	1	NM_004770.3	ENSP00000430846.1

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3213 AN: 152046 Hom.: 100 Cov.: 32

Gnomad AFR AF: 0.0732

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.00543 AC: 1363 AN: 251056 Hom.: 31 AF XY: 0.00398 AC XY: 540 AN XY: 135694

Gnomad AFR exome AF: 0.0730

Gnomad AMR exome AF: 0.00388

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000282

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00228 AC: 3326 AN: 1461828 Hom.: 107 Cov.: 31 AF XY: 0.00196 AC XY: 1427 AN XY: 727212

Gnomad4 AFR exome AF: 0.0767

Gnomad4 AMR exome AF: 0.00416

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000232

Gnomad4 OTH exome AF: 0.00470

GnomAD4 genome AF: 0.0211 AC: 3212 AN: 152164 Hom.: 100 Cov.: 32 AF XY: 0.0209 AC XY: 1554 AN XY: 74392

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.00732

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.00936 Hom.: 8

Bravo AF: 0.0235

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

KCNB2-related disorder Benign:1

Feb 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.1
DANN	Benign	0.65

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: rs34259157; hg19: chr8-73480125;