rs2796051

Positions:

• chr6-73136152-G-A

Variant summary

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

The NM_019842.4(KCNQ5):​c.1468+2511G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,072 control chromosomes in the GnomAD database, including 2,356 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 0.12 (2356 hom., cov: 32)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.288

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]

KCNQ5-AS1 (HGNC:40323): (KCNQ5 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ5	NM_019842.4	c.1468+2511G>A		intron_variant		ENST00000370398.6
KCNQ5-AS1	NR_046621.1	n.225C>T		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ5	ENST00000370398.6	c.1468+2511G>A		intron_variant		1	NM_019842.4	P4
KCNQ5-AS1	ENST00000666538.1	n.518C>T		non_coding_transcript_exon_variant	4/5

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18864 AN: 151946 Hom.: 2358 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0636

Gnomad ASJ AF: 0.0902

Gnomad EAS AF: 0.0547

Gnomad SAS AF: 0.0294

Gnomad FIN AF: 0.0351

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.105

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.124 AC: 18892 AN: 152064 Hom.: 2356 Cov.: 32 AF XY: 0.120 AC XY: 8908 AN XY: 74334

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.0635

Gnomad4 ASJ AF: 0.0902

Gnomad4 EAS AF: 0.0548

Gnomad4 SAS AF: 0.0291

Gnomad4 FIN AF: 0.0351

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0567 Hom.: 525

Bravo AF: 0.136

Asia WGS AF: 0.0640 AC: 223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.3
DANN	Benign	0.56

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: rs2796051; hg19: chr6-73845875;