rs55974552

chr4-40335951-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_017581.4(CHRNA9):c.189G>A(p.Thr63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,612,528 control chromosomes in the GnomAD database, including 197 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 0.013 (21 hom., cov: 32)
  • Exomes 𝑓: 0.014 (176 hom.)
• Consequence: CHRNA9 NM_017581.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80

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=-0.67).
• BP7: Synonymous conserved (PhyloP=-1.8 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.013 (1975/152274) while in subpopulation AMR AF= 0.0247 (378/15292). AF 95% confidence interval is 0.0227. There are 21 homozygotes in gnomad4. There are 971 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA9	NM_017581.4	c.189G>A	p.Thr63=	synonymous_variant	2/5	ENST00000310169.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA9	ENST00000310169.3	c.189G>A	p.Thr63=	synonymous_variant	2/5	1	NM_017581.4	P1

Frequencies

GnomAD3 genomes AF: 0.0130 AC: 1977 AN: 152156 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00314

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0248

Gnomad ASJ AF: 0.0335

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00773

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0172

Gnomad OTH AF: 0.0206

GnomAD3 exomes AF: 0.0136 AC: 3422 AN: 251266 Hom.: 29 AF XY: 0.0145 AC XY: 1970 AN XY: 135792

Gnomad AFR exome AF: 0.00271

Gnomad AMR exome AF: 0.0156

Gnomad ASJ exome AF: 0.0298

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00814

Gnomad FIN exome AF: 0.00722

Gnomad NFE exome AF: 0.0179

Gnomad OTH exome AF: 0.0170

GnomAD4 exome AF: 0.0141 AC: 20618 AN: 1460254 Hom.: 176 Cov.: 30 AF XY: 0.0143 AC XY: 10387 AN XY: 726524

Gnomad4 AFR exome AF: 0.00397

Gnomad4 AMR exome AF: 0.0164

Gnomad4 ASJ exome AF: 0.0305

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00808

Gnomad4 FIN exome AF: 0.00876

Gnomad4 NFE exome AF: 0.0148

Gnomad4 OTH exome AF: 0.0166

GnomAD4 genome AF: 0.0130 AC: 1975 AN: 152274 Hom.: 21 Cov.: 32 AF XY: 0.0130 AC XY: 971 AN XY: 74460

Gnomad4 AFR AF: 0.00313

Gnomad4 AMR AF: 0.0247

Gnomad4 ASJ AF: 0.0335

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00643

Gnomad4 FIN AF: 0.00773

Gnomad4 NFE AF: 0.0172

Gnomad4 OTH AF: 0.0203

Alfa AF: 0.0154 Hom.: 9

Bravo AF: 0.0143

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0212

EpiControl AF: 0.0235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
Cadd	Benign	0.93
Dann	Benign	0.70

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: rs55974552; hg19: chr4-40337968;