rs56171884

Variant names:

• chr4-40335960-G-A
• rs56171884
• NM_017581.4:c.198G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_017581.4(CHRNA9):​c.198G>A​(p.Gln66Gln) 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

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA9	NM_017581.4	c.198G>A	p.Gln66Gln	synonymous_variant	Exon 2 of 5	ENST00000310169.3	NP_060051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3	c.198G>A	p.Gln66Gln	synonymous_variant	Exon 2 of 5	1	NM_017581.4	ENSP00000312663.2

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

GnomAD2 exomes AF: 0.00213 AC: 536 AN: 251210 AF XY: 0.00216

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 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 AC: 24 AN: 33472

Gnomad4 AMR exome AF: 0.00170 AC: 76 AN: 44716

Gnomad4 ASJ exome AF: 0.00111 AC: 29 AN: 26124

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39700

Gnomad4 SAS exome AF: 0.000220 AC: 19 AN: 86200

Gnomad4 FIN exome AF: 0.000243 AC: 13 AN: 53398

Gnomad4 NFE exome AF: 0.00413 AC: 4587 AN: 1110818

Gnomad4 Remaining exome AF: 0.00217 AC: 131 AN: 60362

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 AC: 0.000577478 AN: 0.000577478

Gnomad4 AMR AF: 0.00157 AC: 0.0015676 AN: 0.0015676

Gnomad4 ASJ AF: 0.00173 AC: 0.00172811 AN: 0.00172811

Gnomad4 EAS AF: 0.000193 AC: 0.00019305 AN: 0.00019305

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.000283 AC: 0.000282646 AN: 0.000282646

Gnomad4 NFE AF: 0.00351 AC: 0.00351305 AN: 0.00351305

Gnomad4 OTH AF: 0.00142 AC: 0.00142045 AN: 0.00142045

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
Mutation Taster		=95/5	polymorphism

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;