Variant rs2229961 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000745.4(CHRNA5):c.400G>A(p.Val134Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 1,501,350 control chromosomes in the GnomAD database, including 219 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.010 ( 14 hom., cov: 32)

Exomes 𝑓: 0.015 ( 205 hom. )

Consequence

CHRNA5
NM_000745.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

CHRNA5 (HGNC:1959): (cholinergic receptor nicotinic alpha 5 subunit) The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are thought to be heteropentamers composed of separate but similar subunits. Defects in this gene have been linked to susceptibility to lung cancer type 2 (LNCR2).[provided by RefSeq, Jun 2010]

CHRNA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01397571).

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0103 (1569/152270) while in subpopulation SAS AF= 0.0183 (88/4818). AF 95% confidence interval is 0.0165. There are 14 homozygotes in gnomad4. There are 746 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA5	NM_000745.4 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	4/6	ENST00000299565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CHRNA5	ENST00000299565.9 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	4/6	1	NM_000745.4	P1
CHRNA5	ENST00000394802.4 linkuse as main transcript	c.217G>A	p.Val73Ile	missense_variant	3/5	3
CHRNA5	ENST00000559554.5 linkuse as main transcript	c.400G>A	p.Val134Ile	missense_variant	4/6	3

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1563

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.00255

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.0114

AC:

2450

AN:

214324

Hom.:

AF XY:

0.0127

AC XY:

1477

AN XY:

116584

show subpopulations

Gnomad AFR exome

AF:

0.00326

Gnomad AMR exome

AF:

0.00681

Gnomad ASJ exome

AF:

0.00351

Gnomad EAS exome

AF:

0.0000658

Gnomad SAS exome

AF:

0.0187

Gnomad FIN exome

AF:

0.00314

Gnomad NFE exome

AF:

0.0160

Gnomad OTH exome

AF:

0.0108

GnomAD4 exome

AF:

0.0151

AC:

20364

AN:

1349080

Hom.:

205

Cov.:

AF XY:

0.0151

AC XY:

10098

AN XY:

669670

show subpopulations

Gnomad4 AFR exome

AF:

0.00344

Gnomad4 AMR exome

AF:

0.00687

Gnomad4 ASJ exome

AF:

0.00360

Gnomad4 EAS exome

AF:

0.000107

Gnomad4 SAS exome

AF:

0.0180

Gnomad4 FIN exome

AF:

0.00316

Gnomad4 NFE exome

AF:

0.0170

Gnomad4 OTH exome

AF:

0.0140

GnomAD4 genome

AF:

0.0103

AC:

1569

AN:

152270

Hom.:

Cov.:

AF XY:

0.0100

AC XY:

746

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00308

Gnomad4 AMR

AF:

0.00759

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0183

Gnomad4 FIN

AF:

0.00255

Gnomad4 NFE

AF:

0.0173

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.0139

Hom.:

Bravo

AF:

0.0102

TwinsUK

AF:

0.0183

AC:

ALSPAC

AF:

0.0179

AC:

ESP6500AA

AF:

0.00319

AC:

ESP6500EA

AF:

0.0192

AC:

165

ExAC

AF:

0.0116

AC:

1404

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

D;D

MetaRNN

Benign

0.014

T;T

MetaSVM

Uncertain

0.17

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.88

N;N

REVEL

Uncertain

0.49

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;.

Vest4

0.21

MPC

0.73

ClinPred

0.042

GERP RS

5.1

Varity_R

0.75

gMVP

0.32

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