rs947612

Variant names:

• chr6-73028938-G-A
• rs947612
• NM_019842.4:c.490-12998G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019842.4(KCNQ5):​c.490-12998G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,956 control chromosomes in the GnomAD database, including 29,079 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 0.58 (29079 hom., cov: 31)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 46

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.490-12998G>A		intron_variant	Intron 2 of 13	ENST00000370398.6	NP_062816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ5	ENST00000370398.6	c.490-12998G>A		intron_variant	Intron 2 of 13	1	NM_019842.4	ENSP00000359425.1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87352 AN: 151838 Hom.: 29080 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.575 AC: 87379 AN: 151956 Hom.: 29079 Cov.: 31 AF XY: 0.575 AC XY: 42674 AN XY: 74272

African (AFR) AF: 0.252 AC: 10437 AN: 41416

American (AMR) AF: 0.589 AC: 8998 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2748 AN: 3472

East Asian (EAS) AF: 0.206 AC: 1063 AN: 5162

South Asian (SAS) AF: 0.669 AC: 3222 AN: 4818

European-Finnish (FIN) AF: 0.729 AC: 7681 AN: 10534

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 50984 AN: 67964

Other (OTH) AF: 0.624 AC: 1316 AN: 2108

Alfa AF: 0.690 Hom.: 167343

Bravo AF: 0.547

Asia WGS AF: 0.431 AC: 1502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.79
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs947612; hg19: chr6-73738661;