dbSNP rs56159866: CHRNA9:p.Val55Val (chr4-40335927-C-T) – 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.165C>T(p.Val55Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,609,194 control chromosomes in the GnomAD database, including 43,439 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 0.17 ( 2844 hom., cov: 32)

Exomes 𝑓: 0.23 ( 40595 hom. )

Consequence

CHRNA9
NM_017581.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.872

Publications

19 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=-0.57).

BP7

Synonymous conserved (PhyloP=-0.872 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA9	NM_017581.4 link	c.165C>T	p.Val55Val	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 link	c.165C>T	p.Val55Val	synonymous_variant	Exon 2 of 5	1	NM_017581.4	ENSP00000312663.2

Frequencies

GnomAD3 genomes

AF:

0.171

AC:

26053

AN:

152024

Hom.:

2847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0453

Gnomad AMI

AF:

0.205

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.135

Gnomad EAS

AF:

0.0529

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.247

Gnomad OTH

AF:

0.180

GnomAD2 exomes

AF:

0.188

AC:

47093

AN:

250768

AF XY:

0.189

show subpopulations

Gnomad AFR exome

AF:

0.0381

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.0501

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.244

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.228

AC:

331884

AN:

1457052

Hom.:

40595

Cov.:

AF XY:

0.225

AC XY:

163189

AN XY:

725042

show subpopulations

African (AFR)

AF:

0.0369

AC:

1234

AN:

33456

American (AMR)

AF:

0.165

AC:

7370

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

3682

AN:

26088

East Asian (EAS)

AF:

0.0455

AC:

1805

AN:

39682

South Asian (SAS)

AF:

0.142

AC:

12242

AN:

86058

European-Finnish (FIN)

AF:

0.231

AC:

12333

AN:

53330

Middle Eastern (MID)

AF:

0.185

AC:

1066

AN:

5756

European-Non Finnish (NFE)

AF:

0.253

AC:

279916

AN:

1107820

Other (OTH)

AF:

0.203

AC:

12236

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

11755

23510

35266

47021

58776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9238

18476

27714

36952

46190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.171

AC:

26048

AN:

152142

Hom.:

2844

Cov.:

AF XY:

0.170

AC XY:

12676

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0452

AC:

1877

AN:

41536

American (AMR)

AF:

0.175

AC:

2669

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.135

AC:

469

AN:

3470

East Asian (EAS)

AF:

0.0532

AC:

276

AN:

5184

South Asian (SAS)

AF:

0.149

AC:

717

AN:

4802

European-Finnish (FIN)

AF:

0.246

AC:

2601

AN:

10570

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.247

AC:

16802

AN:

67976

Other (OTH)

AF:

0.178

AC:

377

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1064

2128

3193

4257

5321

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.216

Hom.:

2008

Bravo

AF:

0.159

Asia WGS

AF:

0.0940

AC:

329

AN:

3478

EpiCase

AF:

0.235

EpiControl

AF:

0.233

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

4.8

(source)

DANN

Benign

0.72

PhyloP100

-0.87

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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