dbSNP rs6447332: CHRNA9:c.211-90G>C (chr4-40337120-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017581.4(CHRNA9):c.211-90G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 1,204,770 control chromosomes in the GnomAD database, including 1,981 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 0.066 ( 485 hom., cov: 33)

Exomes 𝑓: 0.049 ( 1496 hom. )

Consequence

CHRNA9
NM_017581.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.643

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA9	NM_017581.4 link	c.211-90G>C		intron_variant	Intron 2 of 4	ENST00000310169.3	NP_060051.2	Q9UGM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3 link	c.211-90G>C		intron_variant	Intron 2 of 4	1	NM_017581.4	ENSP00000312663.2		Q9UGM1
CHRNA9	ENST00000502377.1 link	n.-166G>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0656

AC:

9979

AN:

152196

Hom.:

485

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0433

Gnomad ASJ

AF:

0.0689

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0364

Gnomad FIN

AF:

0.0141

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0522

Gnomad OTH

AF:

0.0622

GnomAD4 exome

AF:

0.0492

AC:

51731

AN:

1052456

Hom.:

1496

AF XY:

0.0484

AC XY:

25554

AN XY:

528180

show subpopulations

African (AFR)

AF:

0.122

AC:

3081

AN:

25238

American (AMR)

AF:

0.0310

AC:

1054

AN:

34034

Ashkenazi Jewish (ASJ)

AF:

0.0698

AC:

1423

AN:

20374

East Asian (EAS)

AF:

0.000383

AC:

AN:

36510

South Asian (SAS)

AF:

0.0355

AC:

2348

AN:

66116

European-Finnish (FIN)

AF:

0.0161

AC:

802

AN:

49726

Middle Eastern (MID)

AF:

0.0794

AC:

328

AN:

4132

European-Non Finnish (NFE)

AF:

0.0521

AC:

40153

AN:

770286

Other (OTH)

AF:

0.0549

AC:

2528

AN:

46040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

2365

4729

7094

9458

11823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1406

2812

4218

5624

7030

<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:

0.0656

AC:

9986

AN:

152314

Hom.:

485

Cov.:

AF XY:

0.0633

AC XY:

4718

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.120

AC:

4983

AN:

41556

American (AMR)

AF:

0.0431

AC:

660

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0689

AC:

239

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5194

South Asian (SAS)

AF:

0.0360

AC:

174

AN:

4830

European-Finnish (FIN)

AF:

0.0141

AC:

150

AN:

10620

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0522

AC:

3549

AN:

68016

Other (OTH)

AF:

0.0620

AC:

131

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

484

967

1451

1934

2418

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

228

342

456

570

<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:

0.0575

Hom.:

Bravo

AF:

0.0714

Asia WGS

AF:

0.0310

AC:

108

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.3

(source)

DANN

Benign

0.68

PhyloP100

0.64

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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