chr6-72972060-G-A

Position:

• chr6-72972060-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_019842.4(KCNQ5):​c.399-31848G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 152,146 control chromosomes in the GnomAD database, including 59,027 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 0.88 (59027 hom., cov: 31)
• Consequence: KCNQ5 NM_019842.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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]

LOC105377855 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNQ5	NM_019842.4	c.399-31848G>A		intron_variant		ENST00000370398.6
LOC105377855	XR_007059641.1	n.714+3266C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNQ5	ENST00000370398.6	c.399-31848G>A		intron_variant		1	NM_019842.4	P4

Frequencies

GnomAD3 genomes AF: 0.878 AC: 133522 AN: 152028 Hom.: 58994 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.826

Gnomad ASJ AF: 0.920

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.937

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.904

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

GnomAD4 genome AF: 0.878 AC: 133607 AN: 152146 Hom.: 59027 Cov.: 31 AF XY: 0.878 AC XY: 65345 AN XY: 74390

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.920

Gnomad4 EAS AF: 0.802

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.937

Gnomad4 NFE AF: 0.932

Gnomad4 OTH AF: 0.901

Alfa AF: 0.920 Hom.: 129056

Bravo AF: 0.865

Asia WGS AF: 0.824 AC: 2865 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	0.93
DANN	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs9360623; hg19: chr6-73681783;