Variant rs55974552 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_017581.4(CHRNA9):c.189G>A(p.Thr63=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.014 in 1,612,528 control chromosomes in the GnomAD database, including 197 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 0.013 ( 21 hom., cov: 32)

Exomes 𝑓: 0.014 ( 176 hom. )

Consequence

CHRNA9
NM_017581.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.80

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP7

Synonymous conserved (PhyloP=-1.8 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.013 (1975/152274) while in subpopulation AMR AF= 0.0247 (378/15292). AF 95% confidence interval is 0.0227. There are 21 homozygotes in gnomad4. There are 971 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA9	NM_017581.4 linkuse as main transcript	c.189G>A	p.Thr63=	synonymous_variant	2/5	ENST00000310169.3	NP_060051.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA9	ENST00000310169.3 linkuse as main transcript	c.189G>A	p.Thr63=	synonymous_variant	2/5	1	NM_017581.4	ENSP00000312663	P1

Frequencies

GnomAD3 genomes

AF:

0.0130

AC:

1977

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00314

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0248

Gnomad ASJ

AF:

0.0335

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00642

Gnomad FIN

AF:

0.00773

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0172

Gnomad OTH

AF:

0.0206

GnomAD3 exomes

AF:

0.0136

AC:

3422

AN:

251266

Hom.:

AF XY:

0.0145

AC XY:

1970

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.00271

Gnomad AMR exome

AF:

0.0156

Gnomad ASJ exome

AF:

0.0298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00814

Gnomad FIN exome

AF:

0.00722

Gnomad NFE exome

AF:

0.0179

Gnomad OTH exome

AF:

0.0170

GnomAD4 exome

AF:

0.0141

AC:

20618

AN:

1460254

Hom.:

176

Cov.:

AF XY:

0.0143

AC XY:

10387

AN XY:

726524

show subpopulations

Gnomad4 AFR exome

AF:

0.00397

Gnomad4 AMR exome

AF:

0.0164

Gnomad4 ASJ exome

AF:

0.0305

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00808

Gnomad4 FIN exome

AF:

0.00876

Gnomad4 NFE exome

AF:

0.0148

Gnomad4 OTH exome

AF:

0.0166

GnomAD4 genome

AF:

0.0130

AC:

1975

AN:

152274

Hom.:

Cov.:

AF XY:

0.0130

AC XY:

971

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00313

Gnomad4 AMR

AF:

0.0247

Gnomad4 ASJ

AF:

0.0335

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00643

Gnomad4 FIN

AF:

0.00773

Gnomad4 NFE

AF:

0.0172

Gnomad4 OTH

AF:

0.0203

Alfa

AF:

0.0154

Hom.:

Bravo

AF:

0.0143

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0212

EpiControl

AF:

0.0235

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.93

DANN

Benign

0.70

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over