rs3823118

chr6-73173515-G-Achr6-73173515-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.1577+3661G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,034 control chromosomes in the GnomAD database, including 8,730 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 0.26 (8730 hom., cov: 33)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ5	NM_019842.4	c.1577+3661G>A		intron_variant		ENST00000370398.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ5	ENST00000370398.6	c.1577+3661G>A		intron_variant		1	NM_019842.4	P4

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40131 AN: 151916 Hom.: 8695 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.264 AC: 40211 AN: 152034 Hom.: 8730 Cov.: 33 AF XY: 0.267 AC XY: 19876 AN XY: 74330

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.367

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.483

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.0812

Gnomad4 OTH AF: 0.266

Alfa AF: 0.111 Hom.: 2294

Bravo AF: 0.301

Asia WGS AF: 0.355 AC: 1235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.3
Dann	Benign	0.36

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: rs3823118; hg19: chr6-73883238;