rs16827695

Positions:

• chr1-40821382-G-A
• chr1-40821382-G-C
• chr1-40821382-G-T

Variant summary

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

The NM_004700.4(KCNQ4):​c.1042-932G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 152,254 control chromosomes in the GnomAD database, including 488 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 0.069 (488 hom., cov: 33)
• Consequence: KCNQ4 NM_004700.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498

Genes affected

KCNQ4 (HGNC:6298): (potassium voltage-gated channel subfamily Q member 4) The protein encoded by this gene forms a potassium channel that is thought to play a critical role in the regulation of neuronal excitability, particularly in sensory cells of the cochlea. The current generated by this channel is inhibited by M1 muscarinic acetylcholine receptors and activated by retigabine, a novel anti-convulsant drug. The encoded protein can form a homomultimeric potassium channel or possibly a heteromultimeric channel in association with the protein encoded by the KCNQ3 gene. Defects in this gene are a cause of nonsyndromic sensorineural deafness type 2 (DFNA2), an autosomal dominant form of progressive hearing loss. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KCNQ4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNQ4	NM_004700.4	c.1042-932G>A		intron_variant		ENST00000347132.10	NP_004691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNQ4	ENST00000347132.10	c.1042-932G>A		intron_variant		1	NM_004700.4	ENSP00000262916.6
KCNQ4	ENST00000509682.6	c.1042-932G>A		intron_variant		5		ENSP00000423756.2
KCNQ4	ENST00000443478.3	c.727-932G>A		intron_variant		5		ENSP00000406735.3
KCNQ4	ENST00000506017.1	n.361-932G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0691 AC: 10515 AN: 152136 Hom.: 486 Cov.: 33

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.0923

Gnomad AMR AF: 0.0629

Gnomad ASJ AF: 0.0729

Gnomad EAS AF: 0.0533

Gnomad SAS AF: 0.0335

Gnomad FIN AF: 0.0140

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0481

Gnomad OTH AF: 0.0872

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

GnomAD4 genome AF: 0.0691 AC: 10526 AN: 152254 Hom.: 488 Cov.: 33 AF XY: 0.0665 AC XY: 4952 AN XY: 74450

Gnomad4 AFR AF: 0.124

Gnomad4 AMR AF: 0.0627

Gnomad4 ASJ AF: 0.0729

Gnomad4 EAS AF: 0.0525

Gnomad4 SAS AF: 0.0340

Gnomad4 FIN AF: 0.0140

Gnomad4 NFE AF: 0.0481

Gnomad4 OTH AF: 0.0859

Alfa AF: 0.0209 Hom.: 10

Bravo AF: 0.0754

Asia WGS AF: 0.0620 AC: 215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.7
DANN	Benign	0.61

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: rs16827695; hg19: chr1-41287054;