Variant chr4-40349191-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.94

Variant links:

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]

CHRNA9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA9	NM_017581.4 linkuse as main transcript	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 linkuse as main transcript	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.:

Cov.:

show subpopulations

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.:

AF XY:

0.00496

AC XY:

674

AN XY:

135878

show subpopulations

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.:

Cov.:

AF XY:

0.00612

AC XY:

4453

AN XY:

727242

show subpopulations

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.:

Cov.:

AF XY:

0.00478

AC XY:

356

AN XY:

74410

show subpopulations

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.:

Bravo

AF:

0.00359

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00507

EpiControl

AF:

0.00569

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over