chr4-40335927-C-T

Position:

• chr4-40335927-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017581.4(CHRNA9):​c.165C>T​(p.Val55Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,609,194 control chromosomes in the GnomAD database, including 43,439 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 0.17 (2844 hom., cov: 32)
  • Exomes 𝑓: 0.23 (40595 hom.)
• Consequence: CHRNA9 NM_017581.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=-0.872 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA9	NM_017581.4	c.165C>T	p.Val55Val	synonymous_variant	2/5	ENST00000310169.3	NP_060051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3	c.165C>T	p.Val55Val	synonymous_variant	2/5	1	NM_017581.4	ENSP00000312663.2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26053 AN: 152024 Hom.: 2847 Cov.: 32

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.175

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.0529

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.246

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.180

GnomAD3 exomes AF: 0.188 AC: 47093 AN: 250768 Hom.: 5125 AF XY: 0.189 AC XY: 25636 AN XY: 135522

Gnomad AFR exome AF: 0.0381

Gnomad AMR exome AF: 0.165

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.0501

Gnomad SAS exome AF: 0.143

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.244

Gnomad OTH exome AF: 0.210

GnomAD4 exome AF: 0.228 AC: 331884 AN: 1457052 Hom.: 40595 Cov.: 30 AF XY: 0.225 AC XY: 163189 AN XY: 725042

Gnomad4 AFR exome AF: 0.0369

Gnomad4 AMR exome AF: 0.165

Gnomad4 ASJ exome AF: 0.141

Gnomad4 EAS exome AF: 0.0455

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.171 AC: 26048 AN: 152142 Hom.: 2844 Cov.: 32 AF XY: 0.170 AC XY: 12676 AN XY: 74364

Gnomad4 AFR AF: 0.0452

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.135

Gnomad4 EAS AF: 0.0532

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.246

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.178

Alfa AF: 0.216 Hom.: 2008

Bravo AF: 0.159

Asia WGS AF: 0.0940 AC: 329 AN: 3478

EpiCase AF: 0.235

EpiControl AF: 0.233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.8
DANN	Benign	0.72

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: rs56159866; hg19: chr4-40337944; COSMIC: COSV59576696; COSMIC: COSV59576696;