rs56241474

Positions:

• chr4-40335506-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_017581.4(CHRNA9):​c.39C>T​(p.Ile13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 1,610,370 control chromosomes in the GnomAD database, including 66,383 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 0.27 (5893 hom., cov: 33)
  • Exomes 𝑓: 0.28 (60490 hom.)
• Consequence: CHRNA9 NM_017581.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.814

Genes affected

CHRNA9 (HGNC:14079): (cholinergic receptor nicotinic alpha 9 subunit) This gene is a member of the ligand-gated ionic channel family and nicotinic acetylcholine receptor gene superfamily. It encodes a plasma membrane protein that forms homo- or hetero-oligomeric divalent cation channels. This protein is involved in cochlea hair cell development and is also expressed in the outer hair cells (OHCs) of the adult cochlea. [provided by RefSeq, Feb 2012]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA9	NM_017581.4	c.39C>T	p.Ile13=	synonymous_variant	1/5	ENST00000310169.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA9	ENST00000310169.3	c.39C>T	p.Ile13=	synonymous_variant	1/5	1	NM_017581.4	P1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41409 AN: 152044 Hom.: 5885 Cov.: 33

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.0538

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.264

GnomAD3 exomes AF: 0.242 AC: 60702 AN: 251256 Hom.: 7955 AF XY: 0.239 AC XY: 32515 AN XY: 135798

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.216

Gnomad EAS exome AF: 0.0512

Gnomad SAS exome AF: 0.176

Gnomad FIN exome AF: 0.251

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.264

GnomAD4 exome AF: 0.281 AC: 409569 AN: 1458208 Hom.: 60490 Cov.: 31 AF XY: 0.277 AC XY: 200867 AN XY: 725624

Gnomad4 AFR exome AF: 0.291

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.210

Gnomad4 EAS exome AF: 0.0460

Gnomad4 SAS exome AF: 0.175

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.305

Gnomad4 OTH exome AF: 0.266

GnomAD4 genome AF: 0.272 AC: 41448 AN: 152162 Hom.: 5893 Cov.: 33 AF XY: 0.268 AC XY: 19959 AN XY: 74390

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.0542

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.262

Alfa AF: 0.291 Hom.: 3480

Bravo AF: 0.270

Asia WGS AF: 0.134 AC: 467 AN: 3478

EpiCase AF: 0.296

EpiControl AF: 0.288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	8.9
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs56241474; hg19: chr4-40337523; COSMIC: COSV59573737; COSMIC: COSV59573737;