Variant 3-156516319-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_172160.3(KCNAB1):c.915A>G(p.Gly305=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00285 in 1,614,024 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 73 hom. )

Consequence

KCNAB1
NM_172160.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.00

Variant links:

Genes affected

KCNAB1 (HGNC:6228): (potassium voltage-gated channel subfamily A regulatory beta subunit 1) Potassium 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, shaker-related subfamily. This member includes distinct isoforms which are encoded by alternatively spliced transcript variants of this gene. Some of these isoforms are beta subunits, which form heteromultimeric complexes with alpha subunits and modulate the activity of the pore-forming alpha subunits. [provided by RefSeq, Apr 2015]

KCNAB1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 3-156516319-A-G is Benign according to our data. Variant chr3-156516319-A-G is described in ClinVar as [Benign]. Clinvar id is 714984.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00263 (401/152324) while in subpopulation EAS AF= 0.0357 (185/5184). AF 95% confidence interval is 0.0315. There are 9 homozygotes in gnomad4. There are 250 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNAB1	NM_172160.3 linkuse as main transcript	c.915A>G	p.Gly305=	synonymous_variant	11/14	ENST00000490337.6	NP_751892.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNAB1	ENST00000490337.6 linkuse as main transcript	c.915A>G	p.Gly305=	synonymous_variant	11/14	1	NM_172160.3	ENSP00000419952		Q14722-1
	ENST00000661961.1 linkuse as main transcript	n.39-23145A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00264

AC:

402

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0360

Gnomad SAS

AF:

0.0288

Gnomad FIN

AF:

0.00235

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00741

AC:

1863

AN:

251476

Hom.:

AF XY:

0.00814

AC XY:

1106

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0477

Gnomad SAS exome

AF:

0.0289

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.00326

GnomAD4 exome

AF:

0.00288

AC:

4204

AN:

1461700

Hom.:

Cov.:

AF XY:

0.00362

AC XY:

2631

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0312

Gnomad4 SAS exome

AF:

0.0280

Gnomad4 FIN exome

AF:

0.00133

Gnomad4 NFE exome

AF:

0.000161

Gnomad4 OTH exome

AF:

0.00416

GnomAD4 genome

AF:

0.00263

AC:

401

AN:

152324

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

250

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000601

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0357

Gnomad4 SAS

AF:

0.0290

Gnomad4 FIN

AF:

0.00235

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000546

Hom.:

Bravo

AF:

0.00196

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

8.8

DANN

Benign

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over