dbSNP rs55998310: CHRNA9:p.Thr78Thr (chr4-40337233-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_017581.4(CHRNA9):c.234T>C(p.Thr78Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00754 in 1,614,194 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0077 ( 56 hom. )

Consequence

CHRNA9
NM_017581.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.90

Publications

7 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-40337233-T-C is Benign according to our data. Variant chr4-40337233-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2654735.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00772 (11281/1461836) while in subpopulation MID AF = 0.018 (104/5768). AF 95% confidence interval is 0.0152. There are 56 homozygotes in GnomAdExome4. There are 5669 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA9	NM_017581.4 link	c.234T>C	p.Thr78Thr	synonymous_variant	Exon 3 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.234T>C	p.Thr78Thr	synonymous_variant	Exon 3 of 5	1	NM_017581.4	ENSP00000312663.2		Q9UGM1
CHRNA9	ENST00000502377.1 link	n.-53T>C		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00587

AC:

894

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.00807

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00641

Gnomad FIN

AF:

0.00537

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00932

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00640

AC:

1608

AN:

251366

AF XY:

0.00647

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00431

Gnomad ASJ exome

AF:

0.00903

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00684

Gnomad NFE exome

AF:

0.00874

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.00772

AC:

11281

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00780

AC XY:

5669

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.00140

AC:

AN:

33478

American (AMR)

AF:

0.00445

AC:

199

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00930

AC:

243

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.00497

AC:

429

AN:

86252

European-Finnish (FIN)

AF:

0.00711

AC:

380

AN:

53418

Middle Eastern (MID)

AF:

0.0180

AC:

104

AN:

5768

European-Non Finnish (NFE)

AF:

0.00844

AC:

9381

AN:

1111978

Other (OTH)

AF:

0.00823

AC:

497

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

588

1176

1764

2352

2940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.00586

AC:

893

AN:

152358

Hom.:

Cov.:

AF XY:

0.00573

AC XY:

427

AN XY:

74516

show subpopulations

African (AFR)

AF:

0.00144

AC:

AN:

41592

American (AMR)

AF:

0.00470

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00807

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00642

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00537

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00932

AC:

634

AN:

68022

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

129

172

215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00746

Hom.:

Bravo

AF:

0.00516

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00943

EpiControl

AF:

0.0102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CHRNA9: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.13

(source)

DANN

Benign

0.38

PhyloP100

-3.9

Mutation Taster

=100/0

polymorphism

(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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over