rs9351963

chr6-73040138-A-Cchr6-73040138-A-G

Variant summary

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

The NM_019842.4(KCNQ5):c.490-1798A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,152 control chromosomes in the GnomAD database, including 4,106 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 0.18 (4106 hom., cov: 32)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ5	NM_019842.4	c.490-1798A>C		intron_variant		ENST00000370398.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ5	ENST00000370398.6	c.490-1798A>C		intron_variant		1	NM_019842.4	P4

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27978 AN: 152034 Hom.: 4093 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0700

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.184 AC: 28023 AN: 152152 Hom.: 4106 Cov.: 32 AF XY: 0.183 AC XY: 13641 AN XY: 74410

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.0992

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.0700

Gnomad4 NFE AF: 0.0697

Gnomad4 OTH AF: 0.168

Alfa AF: 0.0994 Hom.: 2140

Bravo AF: 0.209

Asia WGS AF: 0.254 AC: 882 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	8.7
Dann	Benign	0.77

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: rs9351963; hg19: chr6-73749861;