rs3823118

Variant names:

• chr6-73173515-G-A
• rs3823118
• NM_019842.4:c.1577+3661G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-73173515-G-A
• chr6-73173515-G-T

Variant summary

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

The NM_019842.4(KCNQ5):​c.1577+3661G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,034 control chromosomes in the GnomAD database, including 8,730 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 0.26 (8730 hom., cov: 33)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 5 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.1577+3661G>A		intron_variant	Intron 11 of 13	ENST00000370398.6	NP_062816.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNQ5	ENST00000370398.6	c.1577+3661G>A		intron_variant	Intron 11 of 13	1	NM_019842.4	ENSP00000359425.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40131 AN: 151916 Hom.: 8695 Cov.: 33

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.0813

Gnomad OTH AF: 0.262

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

GnomAD4 genome AF: 0.264 AC: 40211 AN: 152034 Hom.: 8730 Cov.: 33 AF XY: 0.267 AC XY: 19876 AN XY: 74330

African (AFR) AF: 0.563 AC: 23300 AN: 41410

American (AMR) AF: 0.367 AC: 5616 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3470

East Asian (EAS) AF: 0.483 AC: 2502 AN: 5178

South Asian (SAS) AF: 0.163 AC: 787 AN: 4814

European-Finnish (FIN) AF: 0.126 AC: 1329 AN: 10580

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.0812 AC: 5522 AN: 67976

Other (OTH) AF: 0.266 AC: 562 AN: 2114

Alfa AF: 0.132 Hom.: 4375

Bravo AF: 0.301

Asia WGS AF: 0.355 AC: 1235 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.36
PhyloP100		0.35
Mutation Taster		=98/2	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: rs3823118; hg19: chr6-73883238;