4-40349191-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_017581.4(CHRNA9):c.675G>A(p.Pro225=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00613 in 1,614,098 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0047 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (42 hom.)
• Consequence: CHRNA9 NM_017581.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.94

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 4-40349191-G-A is Benign according to our data. Variant chr4-40349191-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654736.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.94 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA9	NM_017581.4	c.675G>A	p.Pro225=	synonymous_variant	4/5	ENST00000310169.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA9	ENST00000310169.3	c.675G>A	p.Pro225=	synonymous_variant	4/5	1	NM_017581.4	P1

Frequencies

GnomAD3 genomes AF: 0.00468 AC: 712 AN: 152102 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00260

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00673

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.00485 AC: 1220 AN: 251420 Hom.: 10 AF XY: 0.00496 AC XY: 674 AN XY: 135878

Gnomad AFR exome AF: 0.000984

Gnomad AMR exome AF: 0.00104

Gnomad ASJ exome AF: 0.00466

Gnomad EAS exome AF: 0.000435

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.0164

Gnomad NFE exome AF: 0.00640

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00628 AC: 9183 AN: 1461880 Hom.: 42 Cov.: 32 AF XY: 0.00612 AC XY: 4453 AN XY: 727242

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.00432

Gnomad4 EAS exome AF: 0.000403

Gnomad4 SAS exome AF: 0.000510

Gnomad4 FIN exome AF: 0.0164

Gnomad4 NFE exome AF: 0.00696

Gnomad4 OTH exome AF: 0.00518

GnomAD4 genome AF: 0.00468 AC: 713 AN: 152218 Hom.: 3 Cov.: 32 AF XY: 0.00478 AC XY: 356 AN XY: 74410

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00260

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.0156

Gnomad4 NFE AF: 0.00673

Gnomad4 OTH AF: 0.00333

Alfa AF: 0.00537 Hom.: 3

Bravo AF: 0.00359

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00507

EpiControl AF: 0.00569

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

CHRNA9: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.082
Dann	Benign	0.56

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: rs55665751; hg19: chr4-40351208;