11-3666288-C-T

Position:

chr11-3666288-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_020402.4(CHRNA10):c.1172G>A(p.Arg391His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,613,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

CHRNA10
NM_020402.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.512

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.017378569).

BP6

Variant 11-3666288-C-T is Benign according to our data. Variant chr11-3666288-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3267154.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA10	NM_020402.4 linkuse as main transcript	c.1172G>A	p.Arg391His	missense_variant	5/5	ENST00000250699.2	NP_065135.2	Q9GZZ6
CHRNA10	NM_001303034.2 linkuse as main transcript	c.554G>A	p.Arg185His	missense_variant	5/5		NP_001289963.1	Q9GZZ6
CHRNA10	NM_001303035.2 linkuse as main transcript	c.554G>A	p.Arg185His	missense_variant	5/5		NP_001289964.1	Q9GZZ6C4IXS7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHRNA10	ENST00000250699.2 linkuse as main transcript	c.1172G>A	p.Arg391His	missense_variant	5/5	1	NM_020402.4	ENSP00000250699.2	Q9GZZ6
CHRNA10	ENST00000534359 linkuse as main transcript	c.*253G>A		3_prime_UTR_variant	5/5	1		ENSP00000437107.1	E9PNX2
CHRNA10	ENST00000526599.1 linkuse as main transcript	n.*943G>A		non_coding_transcript_exon_variant	5/5	1		ENSP00000432757.1	E9PNT7
CHRNA10	ENST00000526599.1 linkuse as main transcript	n.*943G>A		3_prime_UTR_variant	5/5	1		ENSP00000432757.1	E9PNT7

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

250314

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000315

AC:

AN:

1461116

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000762

Hom.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.065

DANN

Benign

0.88

DEOGEN2

Benign

0.14

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.59

M_CAP

Benign

0.0086

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.41

PrimateAI

Benign

0.29

PROVEAN

Benign

1.3

REVEL

Benign

0.099

Sift

Benign

0.66

Sift4G

Benign

0.59

Polyphen

0.0010

Vest4

0.041

MVP

0.23

MPC

0.16

ClinPred

0.021

GERP RS

-4.8

Varity_R

0.029

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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