rs56171884

chr4-40335960-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017581.4(CHRNA9):c.198G>A(p.Gln66=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00322 in 1,612,864 control chromosomes in the GnomAD database, including 16 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 0.0020 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (14 hom.)
• Consequence: CHRNA9 NM_017581.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA9	NM_017581.4	c.198G>A	p.Gln66=	synonymous_variant	2/5	ENST00000310169.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA9	ENST00000310169.3	c.198G>A	p.Gln66=	synonymous_variant	2/5	1	NM_017581.4	P1

Frequencies

GnomAD3 genomes AF: 0.00197 AC: 300 AN: 152192 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00351

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00213 AC: 536 AN: 251210 Hom.: 0 AF XY: 0.00216 AC XY: 293 AN XY: 135760

Gnomad AFR exome AF: 0.000615

Gnomad AMR exome AF: 0.00133

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000262

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00387

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00335 AC: 4887 AN: 1460554 Hom.: 14 Cov.: 29 AF XY: 0.00323 AC XY: 2349 AN XY: 726658

Gnomad4 AFR exome AF: 0.000717

Gnomad4 AMR exome AF: 0.00170

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000220

Gnomad4 FIN exome AF: 0.000243

Gnomad4 NFE exome AF: 0.00413

Gnomad4 OTH exome AF: 0.00217

GnomAD4 genome AF: 0.00197 AC: 300 AN: 152310 Hom.: 2 Cov.: 32 AF XY: 0.00181 AC XY: 135 AN XY: 74474

Gnomad4 AFR AF: 0.000577

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00351

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00300 Hom.: 3

Bravo AF: 0.00227

EpiCase AF: 0.00491

EpiControl AF: 0.00385

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	10
Dann	Benign	0.67

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: rs56171884; hg19: chr4-40337977;