rs16827695

Variant names:

• chr1-40821382-G-A
• rs16827695
• NM_004700.4:c.1042-932G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 2A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004700.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ4	NM_004700.4	MANE Select	c.1042-932G>A		intron	N/A	NP_004691.2
	KCNQ4	NM_172163.3		c.1042-932G>A		intron	N/A	NP_751895.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNQ4	ENST00000347132.10	TSL:1 MANE Select	c.1042-932G>A		intron	N/A	ENSP00000262916.6
	KCNQ4	ENST00000509682.6	TSL:5	c.1042-932G>A		intron	N/A	ENSP00000423756.2
	KCNQ4	ENST00000443478.3	TSL:5	c.727-932G>A		intron	N/A	ENSP00000406735.3

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

African (AFR) AF: 0.124 AC: 5167 AN: 41528

American (AMR) AF: 0.0627 AC: 960 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0729 AC: 253 AN: 3472

East Asian (EAS) AF: 0.0525 AC: 272 AN: 5184

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4828

European-Finnish (FIN) AF: 0.0140 AC: 149 AN: 10622

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0481 AC: 3271 AN: 68004

Other (OTH) AF: 0.0859 AC: 181 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.7
DANN	Benign	0.61
PhyloP100		-0.50
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: rs16827695; hg19: chr1-41287054;