rs1317538

Variant names:

• chr6-72939688-G-A
• rs1317538
• NM_019842.4:c.399-64220G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.98).
• 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 rank	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.399-64220G>A		intron_variant	Intron 1 of 13	ENST00000370398.6	NP_062816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ5	ENST00000370398.6	c.399-64220G>A		intron_variant	Intron 1 of 13	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

African (AFR) AF: 0.617 AC: 25576 AN: 41450

American (AMR) AF: 0.567 AC: 8665 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1815 AN: 3466

East Asian (EAS) AF: 0.653 AC: 3352 AN: 5132

South Asian (SAS) AF: 0.497 AC: 2391 AN: 4808

European-Finnish (FIN) AF: 0.457 AC: 4817 AN: 10552

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34237 AN: 67950

Other (OTH) AF: 0.524 AC: 1107 AN: 2112

Alfa AF: 0.504 Hom.: 14384

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
PhyloP100		-0.52
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: rs1317538; hg19: chr6-73649411;