rs1317538

Positions:

• chr6-72939688-G-A
• chr6-72939688-G-C

Variant summary

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

The NM_019842.4(KCNQ5):​c.399-64220G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 151,954 control chromosomes in the GnomAD database, including 22,736 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 0.54 (22736 hom., cov: 32)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.517

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.399-64220G>A		intron_variant		ENST00000370398.6	NP_062816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ5	ENST00000370398.6	c.399-64220G>A		intron_variant		1	NM_019842.4	ENSP00000359425.1

Frequencies

GnomAD3 genomes AF: 0.544 AC: 82539 AN: 151836 Hom.: 22719 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.543

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.653

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.457

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.544 AC: 82623 AN: 151954 Hom.: 22736 Cov.: 32 AF XY: 0.545 AC XY: 40440 AN XY: 74258

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.567

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.504

Gnomad4 OTH AF: 0.524

Alfa AF: 0.490 Hom.: 9490

Bravo AF: 0.552

Asia WGS AF: 0.579 AC: 2016 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.26
DANN	Benign	0.51

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: rs1317538; hg19: chr6-73649411;