rs947612

Variant names:

• chr6-73028938-G-A
• rs947612
• NM_019842.4:c.490-12998G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019842.4(KCNQ5):​c.490-12998G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,956 control chromosomes in the GnomAD database, including 29,079 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 0.58 (29079 hom., cov: 31)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

Genes affected

KCNQ5 (HGNC:6299): (potassium voltage-gated channel subfamily Q member 5) This gene is a member of the KCNQ potassium channel gene family that is differentially expressed in subregions of the brain and in skeletal muscle. The protein encoded by this gene yields currents that activate slowly with depolarization and can form heteromeric channels with the protein encoded by the KCNQ3 gene. Currents expressed from this protein have voltage dependences and inhibitor sensitivities in common with M-currents. They are also inhibited by M1 muscarinic receptor activation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.490-12998G>A		intron_variant	Intron 2 of 13	ENST00000370398.6	NP_062816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ5	ENST00000370398.6	c.490-12998G>A		intron_variant	Intron 2 of 13	1	NM_019842.4	ENSP00000359425.1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87352 AN: 151838 Hom.: 29080 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.575 AC: 87379 AN: 151956 Hom.: 29079 Cov.: 31 AF XY: 0.575 AC XY: 42674 AN XY: 74272

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.729

Gnomad4 NFE AF: 0.750

Gnomad4 OTH AF: 0.624

Alfa AF: 0.719 Hom.: 79674

Bravo AF: 0.547

Asia WGS AF: 0.431 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs947612; hg19: chr6-73738661;