rs3757105

Variant names:

• chr6-73183954-G-A
• rs3757105
• NM_019842.4:c.1578-6619G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-73183954-G-A
• chr6-73183954-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.1578-6619G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,086 control chromosomes in the GnomAD database, including 1,086 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 0.11 (1086 hom., cov: 32)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.910
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.1578-6619G>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.1578-6619G>A		intron_variant	Intron 11 of 13	1	NM_019842.4	ENSP00000359425.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16733 AN: 151968 Hom.: 1083 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0715

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.110 AC: 16746 AN: 152086 Hom.: 1086 Cov.: 32 AF XY: 0.113 AC XY: 8368 AN XY: 74344

African (AFR) AF: 0.130 AC: 5385 AN: 41464

American (AMR) AF: 0.176 AC: 2696 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 325 AN: 3472

East Asian (EAS) AF: 0.249 AC: 1284 AN: 5166

South Asian (SAS) AF: 0.132 AC: 632 AN: 4800

European-Finnish (FIN) AF: 0.108 AC: 1139 AN: 10580

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0714 AC: 4858 AN: 68002

Other (OTH) AF: 0.135 AC: 285 AN: 2114

Alfa AF: 0.0838 Hom.: 956

Bravo AF: 0.119

Asia WGS AF: 0.201 AC: 697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.91
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: rs3757105; hg19: chr6-73893677;