dbSNP rs10022491: CHRNA9:p.Ser43Ser (chr4-40335891-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017581.4(CHRNA9):c.129T>C(p.Ser43Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 1,608,422 control chromosomes in the GnomAD database, including 264,161 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 0.65 ( 33428 hom., cov: 32)

Exomes 𝑓: 0.56 ( 230733 hom. )

Consequence

CHRNA9
NM_017581.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.470

Publications

23 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP7

Synonymous conserved (PhyloP=0.47 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA9	NM_017581.4 link	c.129T>C	p.Ser43Ser	synonymous_variant	Exon 2 of 5	ENST00000310169.3	NP_060051.2	Q9UGM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3 link	c.129T>C	p.Ser43Ser	synonymous_variant	Exon 2 of 5	1	NM_017581.4	ENSP00000312663.2		Q9UGM1

Frequencies

GnomAD3 genomes

AF:

0.646

AC:

98166

AN:

151952

Hom.:

33376

Cov.:

show subpopulations

Gnomad AFR

AF:

0.876

Gnomad AMI

AF:

0.737

Gnomad AMR

AF:

0.628

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.408

Gnomad SAS

AF:

0.572

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.630

Gnomad NFE

AF:

0.553

Gnomad OTH

AF:

0.627

GnomAD2 exomes

AF:

0.575

AC:

144236

AN:

250882

AF XY:

0.566

show subpopulations

Gnomad AFR exome

AF:

0.880

Gnomad AMR exome

AF:

0.640

Gnomad ASJ exome

AF:

0.501

Gnomad EAS exome

AF:

0.412

Gnomad FIN exome

AF:

0.562

Gnomad NFE exome

AF:

0.549

Gnomad OTH exome

AF:

0.569

GnomAD4 exome

AF:

0.559

AC:

814446

AN:

1456352

Hom.:

230733

Cov.:

AF XY:

0.558

AC XY:

404057

AN XY:

724734

show subpopulations

African (AFR)

AF:

0.885

AC:

29589

AN:

33420

American (AMR)

AF:

0.635

AC:

28340

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

12913

AN:

26086

East Asian (EAS)

AF:

0.400

AC:

15861

AN:

39680

South Asian (SAS)

AF:

0.569

AC:

49012

AN:

86080

European-Finnish (FIN)

AF:

0.560

AC:

29886

AN:

53364

Middle Eastern (MID)

AF:

0.570

AC:

3279

AN:

5756

European-Non Finnish (NFE)

AF:

0.552

AC:

611415

AN:

1107110

Other (OTH)

AF:

0.567

AC:

34151

AN:

60212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

15483

30966

46448

61931

77414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.646

AC:

98271

AN:

152070

Hom.:

33428

Cov.:

AF XY:

0.643

AC XY:

47809

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.876

AC:

36354

AN:

41500

American (AMR)

AF:

0.627

AC:

9583

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

1719

AN:

3470

East Asian (EAS)

AF:

0.408

AC:

2107

AN:

5158

South Asian (SAS)

AF:

0.570

AC:

2745

AN:

4816

European-Finnish (FIN)

AF:

0.566

AC:

5978

AN:

10558

Middle Eastern (MID)

AF:

0.636

AC:

187

AN:

294

European-Non Finnish (NFE)

AF:

0.553

AC:

37605

AN:

67972

Other (OTH)

AF:

0.628

AC:

1325

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1655

3310

4964

6619

8274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.589

Hom.:

43175

Bravo

AF:

0.660

Asia WGS

AF:

0.525

AC:

1823

AN:

3478

EpiCase

AF:

0.551

EpiControl

AF:

0.543

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.66

PhyloP100

0.47

Mutation Taster

=84/16

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs10022491

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over