rs9351963

Variant names:

• chr6-73040138-A-C
• rs9351963
• NM_019842.4:c.490-1798A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-73040138-A-C
• chr6-73040138-A-G
• chr6-73040138-A-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.490-1798A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,152 control chromosomes in the GnomAD database, including 4,106 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 0.18 (4106 hom., cov: 32)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 4 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 = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNQ5	NM_019842.4	c.490-1798A>C		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.490-1798A>C		intron_variant	Intron 2 of 13	1	NM_019842.4	ENSP00000359425.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27978 AN: 152034 Hom.: 4093 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.0992

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0700

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0697

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.184 AC: 28023 AN: 152152 Hom.: 4106 Cov.: 32 AF XY: 0.183 AC XY: 13641 AN XY: 74410

African (AFR) AF: 0.388 AC: 16085 AN: 41476

American (AMR) AF: 0.215 AC: 3292 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0992 AC: 344 AN: 3466

East Asian (EAS) AF: 0.344 AC: 1775 AN: 5166

South Asian (SAS) AF: 0.130 AC: 629 AN: 4824

European-Finnish (FIN) AF: 0.0700 AC: 743 AN: 10618

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0697 AC: 4741 AN: 68004

Other (OTH) AF: 0.168 AC: 354 AN: 2112

Alfa AF: 0.113 Hom.: 6635

Bravo AF: 0.209

Asia WGS AF: 0.254 AC: 882 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	8.7
DANN	Benign	0.77
PhyloP100		1.3
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: rs9351963; hg19: chr6-73749861;