Variant 11-3667573-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020402.4(CHRNA10):c.554G>A(p.Arg185Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000988 in 1,558,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000094 ( 0 hom. )

Consequence

CHRNA10
NM_020402.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.706

Variant links:

Genes affected

CHRNA10 (HGNC:13800): (cholinergic receptor nicotinic alpha 10 subunit) Predicted to enable acetylcholine-gated cation-selective channel activity. Acts upstream of or within positive regulation of cytosolic calcium ion concentration. Predicted to be located in membrane. Predicted to be active in cholinergic synapse and neuron projection. Predicted to be integral component of postsynaptic specialization membrane. [provided by Alliance of Genome Resources, Apr 2022]

CHRNA10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040310025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CHRNA10	NM_020402.4 linkuse as main transcript	c.554G>A	p.Arg185Gln	missense_variant	4/5	ENST00000250699.2
CHRNA10	NM_001303034.2 linkuse as main transcript	c.-65G>A		5_prime_UTR_variant	4/5
CHRNA10	NM_001303035.2 linkuse as main transcript	c.-65G>A		5_prime_UTR_variant	4/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CHRNA10	ENST00000250699.2 linkuse as main transcript	c.554G>A	p.Arg185Gln	missense_variant	4/5	1	NM_020402.4	P1
CHRNA10	ENST00000534359.1 linkuse as main transcript	c.7G>A	p.Gly3Ser	missense_variant	4/5	1
CHRNA10	ENST00000526599.1 linkuse as main transcript	c.*325G>A		3_prime_UTR_variant, NMD_transcript_variant	4/5	1

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000899

AC:

AN:

155784

Hom.:

AF XY:

0.0000348

AC XY:

AN XY:

86276

show subpopulations

Gnomad AFR exome

AF:

0.000120

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000145

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000939

AC:

132

AN:

1405794

Hom.:

Cov.:

AF XY:

0.0000876

AC XY:

AN XY:

696574

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.000385

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000543

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000817

Gnomad4 OTH exome

AF:

0.000376

GnomAD4 genome

AF:

0.000144

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000153

Hom.:

Bravo

AF:

0.000208

ExAC

AF:

0.0000617

AC:

Asia WGS

AF:

0.000290

AC:

AN:

3462

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2022

The c.554G>A (p.R185Q) alteration is located in exon 4 (coding exon 4) of the CHRNA10 gene. This alteration results from a G to A substitution at nucleotide position 554, causing the arginine (R) at amino acid position 185 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.97

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.34

M_CAP

Uncertain

0.091

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.95

MutationTaster

Benign

1.0

N;N

PROVEAN

Pathogenic

-6.0

REVEL

Benign

0.15

Sift4G

Benign

0.54

Vest4

0.30

MVP

0.54

ClinPred

0.011

GERP RS

2.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over