Variant rs56210055 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017581.4(CHRNA9):c.934G>A(p.Ala312Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00579 in 1,611,654 control chromosomes in the GnomAD database, including 254 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 0.022 ( 104 hom., cov: 33)

Exomes 𝑓: 0.0041 ( 150 hom. )

Consequence

CHRNA9
NM_017581.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.60

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:

CHRNA9 (HGNC:):

CHRNA9 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009749055).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA9	NM_017581.4 linkuse as main transcript	c.934G>A	p.Ala312Thr	missense_variant	5/5	ENST00000310169.3	NP_060051.2	Q9UGM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3 linkuse as main transcript	c.934G>A	p.Ala312Thr	missense_variant	5/5	1	NM_017581.4	ENSP00000312663.2		Q9UGM1
CHRNA9	ENST00000509518.1 linkuse as main transcript	n.385G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3349

AN:

152204

Hom.:

104

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0706

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.000999

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.00928

AC:

2306

AN:

248596

Hom.:

AF XY:

0.00820

AC XY:

1103

AN XY:

134438

show subpopulations

Gnomad AFR exome

AF:

0.0688

Gnomad AMR exome

AF:

0.00839

Gnomad ASJ exome

AF:

0.00812

Gnomad EAS exome

AF:

0.00343

Gnomad SAS exome

AF:

0.0185

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00111

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.00409

AC:

5969

AN:

1459332

Hom.:

150

Cov.:

AF XY:

0.00433

AC XY:

3141

AN XY:

725512

show subpopulations

Gnomad4 AFR exome

AF:

0.0705

Gnomad4 AMR exome

AF:

0.00904

Gnomad4 ASJ exome

AF:

0.00829

Gnomad4 EAS exome

AF:

0.00144

Gnomad4 SAS exome

AF:

0.0187

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000615

Gnomad4 OTH exome

AF:

0.00908

GnomAD4 genome

AF:

0.0220

AC:

3357

AN:

152322

Hom.:

104

Cov.:

AF XY:

0.0215

AC XY:

1605

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0706

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00308

Gnomad4 SAS

AF:

0.0212

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.00400

Hom.:

Bravo

AF:

0.0241

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.0670

AC:

295

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.0110

AC:

1333

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0097

MetaSVM

Benign

-0.44

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.61

Sift

Benign

0.052

Sift4G

Benign

0.41

Polyphen

0.88

Vest4

0.29

MPC

0.35

ClinPred

0.039

GERP RS

5.7

Varity_R

0.45

gMVP

0.71

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over