rs2000203

Positions:

• chr6-72987343-G-A
• chr6-72987343-G-C
• chr6-72987343-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.399-16565G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 699,616 control chromosomes in the GnomAD database, including 120,030 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 0.52 (22800 hom., cov: 31)
  • Exomes 𝑓: 0.57 (97230 hom.)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.756

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]

KNOP1P4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.399-16565G>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.399-16565G>A		intron_variant		1	NM_019842.4	ENSP00000359425.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78934 AN: 151872 Hom.: 22798 Cov.: 31

Gnomad AFR AF: 0.273

Gnomad AMI AF: 0.807

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.586

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.571

GnomAD4 exome AF: 0.574 AC: 314365 AN: 547626 Hom.: 97230 Cov.: 3 AF XY: 0.585 AC XY: 175857 AN XY: 300356

Gnomad4 AFR exome AF: 0.215

Gnomad4 AMR exome AF: 0.483

Gnomad4 ASJ exome AF: 0.709

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.631

Gnomad4 FIN exome AF: 0.582

Gnomad4 NFE exome AF: 0.615

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.519 AC: 78948 AN: 151990 Hom.: 22800 Cov.: 31 AF XY: 0.519 AC XY: 38533 AN XY: 74286

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.291

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.587

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.572

Alfa AF: 0.548 Hom.: 3724

Bravo AF: 0.501

Asia WGS AF: 0.432 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	7.6
DANN	Uncertain	0.98

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: rs2000203; hg19: chr6-73697066; COSMIC: COSV59647904;