rs16883476

Variant names:

• chr6-73185818-A-G
• rs16883476
• NM_019842.4:c.1578-4755A>G

Variant summary

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

The NM_019842.4(KCNQ5):​c.1578-4755A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,200 control chromosomes in the GnomAD database, including 4,038 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 0.22 (4038 hom., cov: 32)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.179
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.1578-4755A>G		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.1578-4755A>G		intron_variant	Intron 11 of 13	1	NM_019842.4	ENSP00000359425.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34061 AN: 152082 Hom.: 4037 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.224 AC: 34069 AN: 152200 Hom.: 4038 Cov.: 32 AF XY: 0.223 AC XY: 16562 AN XY: 74420

African (AFR) AF: 0.161 AC: 6673 AN: 41538

American (AMR) AF: 0.258 AC: 3936 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1067 AN: 3468

East Asian (EAS) AF: 0.221 AC: 1144 AN: 5174

South Asian (SAS) AF: 0.168 AC: 812 AN: 4826

European-Finnish (FIN) AF: 0.242 AC: 2566 AN: 10596

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16769 AN: 68006

Other (OTH) AF: 0.261 AC: 549 AN: 2104

Alfa AF: 0.243 Hom.: 14946

Bravo AF: 0.227

Asia WGS AF: 0.214 AC: 743 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.42
PhyloP100		-0.18
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: rs16883476; hg19: chr6-73895541;