rs7744813

Positions:

• chr6-72933566-C-A
• chr6-72933566-C-G
• chr6-72933566-C-T

Variant summary

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

The NM_019842.4(KCNQ5):​c.399-70342C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 151,964 control chromosomes in the GnomAD database, including 33,321 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 0.66 (33321 hom., cov: 32)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ5	NM_019842.4	c.399-70342C>A		intron_variant		ENST00000370398.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ5	ENST00000370398.6	c.399-70342C>A		intron_variant		1	NM_019842.4	P4

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99619 AN: 151846 Hom.: 33270 Cov.: 32

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.656

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.642

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.656 AC: 99726 AN: 151964 Hom.: 33321 Cov.: 32 AF XY: 0.655 AC XY: 48631 AN XY: 74250

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.677

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.790

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.631

Alfa AF: 0.631 Hom.: 12579

Bravo AF: 0.673

Asia WGS AF: 0.623 AC: 2167 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.9
DANN	Benign	0.80

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: rs7744813; hg19: chr6-73643289;