rs41272419

Variant names:

• chr8-72567905-C-G
• rs41272419
• NM_004770.3:c.171C>G

Your query was ambiguous. Multiple possible variants found:

• chr8-72567905-C-G
• chr8-72567905-C-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_004770.3(KCNB2):​c.171C>G​(p.Pro57Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0272 in 1,613,918 control chromosomes in the GnomAD database, including 981 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (143 hom., cov: 32)
  • Exomes 𝑓: 0.026 (838 hom.)
• Consequence: KCNB2 NM_004770.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.172
• Publications: 3 publications found

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]

KCNB2 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 8-72567905-C-G is Benign according to our data. Variant chr8-72567905-C-G is described in ClinVar as Benign. ClinVar VariationId is 1282555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.172 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0852 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004770.3. 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
	KCNB2	NM_004770.3	MANE Select	c.171C>G	p.Pro57Pro	synonymous	Exon 2 of 3	NP_004761.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNB2	ENST00000523207.2	TSL:1 MANE Select	c.171C>G	p.Pro57Pro	synonymous	Exon 2 of 3	ENSP00000430846.1	Q92953

Frequencies

GnomAD3 genomes AF: 0.0357 AC: 5425 AN: 152076 Hom.: 144 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0283

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.0270

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0368

GnomAD2 exomes AF: 0.0358 AC: 8990 AN: 250796 AF XY: 0.0373

Gnomad AFR exome AF: 0.0630

Gnomad AMR exome AF: 0.0495

Gnomad ASJ exome AF: 0.0340

Gnomad EAS exome AF: 0.000490

Gnomad FIN exome AF: 0.0274

Gnomad NFE exome AF: 0.0220

Gnomad OTH exome AF: 0.0281

GnomAD4 exome AF: 0.0263 AC: 38438 AN: 1461724 Hom.: 838 Cov.: 31 AF XY: 0.0281 AC XY: 20441 AN XY: 727152

African (AFR) AF: 0.0643 AC: 2153 AN: 33472

American (AMR) AF: 0.0480 AC: 2147 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0311 AC: 813 AN: 26122

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.0873 AC: 7523 AN: 86214

European-Finnish (FIN) AF: 0.0263 AC: 1404 AN: 53408

Middle Eastern (MID) AF: 0.0388 AC: 224 AN: 5766

European-Non Finnish (NFE) AF: 0.0203 AC: 22591 AN: 1111944

Other (OTH) AF: 0.0260 AC: 1571 AN: 60386

GnomAD4 genome AF: 0.0357 AC: 5430 AN: 152194 Hom.: 143 Cov.: 32 AF XY: 0.0367 AC XY: 2728 AN XY: 74408

African (AFR) AF: 0.0624 AC: 2593 AN: 41528

American (AMR) AF: 0.0285 AC: 435 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5158

South Asian (SAS) AF: 0.0923 AC: 445 AN: 4820

European-Finnish (FIN) AF: 0.0270 AC: 286 AN: 10596

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0217 AC: 1479 AN: 68020

Other (OTH) AF: 0.0360 AC: 76 AN: 2112

Alfa AF: 0.0191 Hom.: 11

Bravo AF: 0.0350

Asia WGS AF: 0.0350 AC: 121 AN: 3478

EpiCase AF: 0.0204

EpiControl AF: 0.0248

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	KCNB2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.6
DANN	Benign	0.73
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs41272419; hg19: chr8-73480140;