Genetic Variant CHRNA9:c.64+18C>T (chr4-40335549-C-T) – 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.64+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,589,974 control chromosomes in the GnomAD database, including 40,307 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 0.21 ( 3715 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36592 hom. )

Consequence

CHRNA9
NM_017581.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

9 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:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017581.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA9	NM_017581.4	MANE Select	c.64+18C>T		intron	N/A	NP_060051.2	Q9UGM1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA9	ENST00000310169.3	TSL:1 MANE Select	c.64+18C>T		intron	N/A	ENSP00000312663.2	Q9UGM1

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32431

AN:

152076

Hom.:

3718

Cov.:

show subpopulations

Gnomad AFR

AF:

0.145

Gnomad AMI

AF:

0.430

Gnomad AMR

AF:

0.309

Gnomad ASJ

AF:

0.227

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.255

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.219

GnomAD2 exomes

AF:

0.235

AC:

59087

AN:

251016

AF XY:

0.233

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.365

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.232

GnomAD4 exome

AF:

0.222

AC:

319329

AN:

1437780

Hom.:

36592

Cov.:

AF XY:

0.222

AC XY:

159173

AN XY:

717054

show subpopulations

African (AFR)

AF:

0.141

AC:

4662

AN:

33042

American (AMR)

AF:

0.356

AC:

15890

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

5679

AN:

26000

East Asian (EAS)

AF:

0.170

AC:

6722

AN:

39634

South Asian (SAS)

AF:

0.204

AC:

17498

AN:

85810

European-Finnish (FIN)

AF:

0.300

AC:

16009

AN:

53394

Middle Eastern (MID)

AF:

0.233

AC:

1322

AN:

5672

European-Non Finnish (NFE)

AF:

0.219

AC:

238266

AN:

1089986

Other (OTH)

AF:

0.223

AC:

13281

AN:

59600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

11831

23663

35494

47326

59157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8106

16212

24318

32424

40530

<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:

0.213

AC:

32438

AN:

152194

Hom.:

3715

Cov.:

AF XY:

0.216

AC XY:

16065

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.145

AC:

6025

AN:

41544

American (AMR)

AF:

0.309

AC:

4723

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.227

AC:

789

AN:

3470

East Asian (EAS)

AF:

0.145

AC:

750

AN:

5190

South Asian (SAS)

AF:

0.196

AC:

947

AN:

4830

European-Finnish (FIN)

AF:

0.297

AC:

3134

AN:

10562

Middle Eastern (MID)

AF:

0.260

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.223

AC:

15144

AN:

67992

Other (OTH)

AF:

0.217

AC:

460

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1323

2646

3970

5293

6616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

330

660

990

1320

1650

<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:

0.215

Hom.:

2195

Bravo

AF:

0.212

Asia WGS

AF:

0.163

AC:

565

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.0

(source)

DANN

Benign

0.65

PhyloP100

-1.1

PromoterAI

-0.12

Neutral

(source)

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over