chr3-156120848-C-T

Variant names:

• chr3-156120848-C-T
• rs9812862
• NM_172160.3:c.237C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_172160.3(KCNAB1):​c.237C>T​(p.Ser79Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,614,154 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (66 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (60 hom.)
• Consequence: KCNAB1 NM_172160.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.158
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 3-156120848-C-T is Benign according to our data. Variant chr3-156120848-C-T is described in ClinVar as Benign. ClinVar VariationId is 786023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.158 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0513 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172160.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNAB1	NM_172160.3	MANE Select	c.237C>T	p.Ser79Ser	synonymous	Exon 1 of 14	NP_751892.1	Q14722-1
	KCNAB1	NM_001308217.1		c.237C>T	p.Ser79Ser	synonymous	Exon 1 of 13	NP_001295146.1	Q14722

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNAB1	ENST00000490337.6	TSL:1 MANE Select	c.237C>T	p.Ser79Ser	synonymous	Exon 1 of 14	ENSP00000419952.1	Q14722-1
	KCNAB1	ENST00000389636.9	TSL:2	c.237C>T	p.Ser79Ser	synonymous	Exon 1 of 13	ENSP00000374287.5	B7Z8E5
	KCNAB1	ENST00000472028.5	TSL:4	c.29+2509C>T		intron	N/A	ENSP00000420755.1	C9JBV8

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2315 AN: 152196 Hom.: 65 Cov.: 33

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00471

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.0139

GnomAD2 exomes AF: 0.00393 AC: 985 AN: 250624 AF XY: 0.00287

Gnomad AFR exome AF: 0.0532

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000186

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00162 AC: 2371 AN: 1461840 Hom.: 60 Cov.: 31 AF XY: 0.00137 AC XY: 995 AN XY: 727224

African (AFR) AF: 0.0562 AC: 1882 AN: 33480

American (AMR) AF: 0.00288 AC: 129 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86256

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53376

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5764

European-Non Finnish (NFE) AF: 0.0000899 AC: 100 AN: 1112010

Other (OTH) AF: 0.00378 AC: 228 AN: 60396

GnomAD4 genome AF: 0.0153 AC: 2327 AN: 152314 Hom.: 66 Cov.: 33 AF XY: 0.0151 AC XY: 1125 AN XY: 74496

African (AFR) AF: 0.0532 AC: 2210 AN: 41562

American (AMR) AF: 0.00470 AC: 72 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68026

Other (OTH) AF: 0.0137 AC: 29 AN: 2114

Alfa AF: 0.00805 Hom.: 18

Bravo AF: 0.0179

Asia WGS AF: 0.00260 AC: 10 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	9.7
DANN	Benign	0.88
PhyloP100		-0.16
PromoterAI		-0.027	Neutral
Mutation Taster		=94/6	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs9812862; hg19: chr3-155838637;