rs1347696

Variant names:

• chr8-132154956-G-C
• rs1347696
• NM_004519.4:c.1262+8512C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004519.4(KCNQ3):​c.1262+8512C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,906 control chromosomes in the GnomAD database, including 18,341 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18341 hom., cov: 31)
• Consequence: KCNQ3 NM_004519.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• Publications: 1 publications found

Genes affected

KCNQ3 (HGNC:6297): (potassium voltage-gated channel subfamily Q member 3) This gene encodes a protein that functions in the regulation of neuronal excitability. The encoded protein forms an M-channel by associating with the products of the related KCNQ2 or KCNQ5 genes, which both encode integral membrane proteins. M-channel currents are inhibited by M1 muscarinic acetylcholine receptors and are activated by retigabine, a novel anti-convulsant drug. Defects in this gene are a cause of benign familial neonatal convulsions type 2 (BFNC2), also known as epilepsy, benign neonatal type 2 (EBN2). Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, May 2014]

KCNQ3 Gene-Disease associations (from GenCC):

• seizures, benign familial neonatal, 2

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• benign familial infantile epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• benign neonatal seizures

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ3	NM_004519.4	c.1262+8512C>G		intron_variant	Intron 9 of 14	ENST00000388996.10	NP_004510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ3	ENST00000388996.10	c.1262+8512C>G		intron_variant	Intron 9 of 14	1	NM_004519.4	ENSP00000373648.3

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74102 AN: 151788 Hom.: 18325 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.472

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.482

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.524

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.488 AC: 74155 AN: 151906 Hom.: 18341 Cov.: 31 AF XY: 0.483 AC XY: 35892 AN XY: 74238

African (AFR) AF: 0.455 AC: 18851 AN: 41396

American (AMR) AF: 0.472 AC: 7217 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1416 AN: 3470

East Asian (EAS) AF: 0.482 AC: 2479 AN: 5142

South Asian (SAS) AF: 0.256 AC: 1229 AN: 4810

European-Finnish (FIN) AF: 0.529 AC: 5591 AN: 10570

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.526 AC: 35700 AN: 67934

Other (OTH) AF: 0.521 AC: 1099 AN: 2108

Alfa AF: 0.513 Hom.: 2483

Bravo AF: 0.494

Asia WGS AF: 0.390 AC: 1356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.8
DANN	Benign	0.57
PhyloP100		-0.18
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: rs1347696; hg19: chr8-133167203;