3-156120712-C-G

Variant names:

• chr3-156120712-C-G
• rs144052895
• NM_172160.3:c.101C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_172160.3(KCNAB1):​c.101C>G​(p.Ser34Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000395 in 1,614,220 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: KCNAB1 NM_172160.3 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.08

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0054148734).
• BP6: Variant 3-156120712-C-G is Benign according to our data. Variant chr3-156120712-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 724340.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNAB1	NM_172160.3	c.101C>G	p.Ser34Cys	missense_variant	Exon 1 of 14	ENST00000490337.6	NP_751892.1
KCNAB1	NM_001308217.1	c.101C>G	p.Ser34Cys	missense_variant	Exon 1 of 13		NP_001295146.1
KCNAB1	XM_017007174.3	c.101C>G	p.Ser34Cys	missense_variant	Exon 1 of 9		XP_016862663.1
KCNAB1	XM_017007171.3	c.29+2373C>G		intron_variant	Intron 1 of 13		XP_016862660.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNAB1	ENST00000490337.6	c.101C>G	p.Ser34Cys	missense_variant	Exon 1 of 14	1	NM_172160.3	ENSP00000419952.1

Frequencies

GnomAD3 genomes AF: 0.00220 AC: 335 AN: 152208 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00736

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.000501 AC: 126 AN: 251472 Hom.: 1 AF XY: 0.000368 AC XY: 50 AN XY: 135912

Gnomad AFR exome AF: 0.00683

Gnomad AMR exome AF: 0.000405

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000207 AC: 302 AN: 1461894 Hom.: 1 Cov.: 31 AF XY: 0.000188 AC XY: 137 AN XY: 727248

Gnomad4 AFR exome AF: 0.00738

Gnomad4 AMR exome AF: 0.000537

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.000464

GnomAD4 genome AF: 0.00221 AC: 336 AN: 152326 Hom.: 1 Cov.: 33 AF XY: 0.00209 AC XY: 156 AN XY: 74492

Gnomad4 AFR AF: 0.00736

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.000327 Hom.: 0

Bravo AF: 0.00236

ESP6500AA AF: 0.00567 AC: 25

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000651 AC: 79

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.079	T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.0054	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.27	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.087	T;T
Polyphen		0.98	D;D
Vest4		0.24
MVP		0.42
MPC		0.65
ClinPred		0.054	T
GERP RS		5.5
Varity_R		0.17
gMVP		0.25

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs144052895; hg19: chr3-155838501;