rs3757105

chr6-73183954-G-Achr6-73183954-G-T

Variant summary

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

The NM_019842.4(KCNQ5):c.1578-6619G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,086 control chromosomes in the GnomAD database, including 1,086 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 0.11 (1086 hom., cov: 32)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ5	NM_019842.4	c.1578-6619G>A		intron_variant		ENST00000370398.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ5	ENST00000370398.6	c.1578-6619G>A		intron_variant		1	NM_019842.4	P4

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16733 AN: 151968 Hom.: 1083 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.110 AC: 16746 AN: 152086 Hom.: 1086 Cov.: 32 AF XY: 0.113 AC XY: 8368 AN XY: 74344

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.0936

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0714

Gnomad4 OTH AF: 0.135

Alfa AF: 0.0796 Hom.: 698

Bravo AF: 0.119

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.1
Dann	Benign	0.52

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: rs3757105; hg19: chr6-73893677;