Variant chr8-42765177-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004198.3(CHRNA6):c.107G>C(p.Arg36Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000835 in 1,614,126 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00080 ( 3 hom. )

Consequence

CHRNA6
NM_004198.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.781

Variant links:

Genes affected

CHRNA6 (HGNC:15963): (cholinergic receptor nicotinic alpha 6 subunit) This gene encodes an alpha subunit of neuronal nicotinic acetylcholine receptors. These receptors consist of five subunits and function as ion channels involved in neurotransmission. The encoded protein is a subunit of neuronal nicotinic acetylcholine receptors that mediate dopaminergic neurotransmission and are activated by acetylcholine and exogenous nicotine. Alternatively spliced transcript variants have been observed for this gene. Single nucleotide polymorphisms in this gene have been associated with both nicotine and alcohol dependence. [provided by RefSeq, Dec 2010]

CHRNA6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.023948044).

BP6

Variant 8-42765177-C-G is Benign according to our data. Variant chr8-42765177-C-G is described in ClinVar as [Benign]. Clinvar id is 733850.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHRNA6	NM_004198.3 linkuse as main transcript	c.107G>C	p.Arg36Thr	missense_variant	2/6	ENST00000276410.7	NP_004189.1
CHRNA6	NM_001199279.1 linkuse as main transcript	c.107G>C	p.Arg36Thr	missense_variant	2/5		NP_001186208.1
CHRNA6	XM_047422396.1 linkuse as main transcript	c.107G>C	p.Arg36Thr	missense_variant	3/7		XP_047278352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000276410.7 linkuse as main transcript	c.107G>C	p.Arg36Thr	missense_variant	2/6	1	NM_004198.3	ENSP00000276410	P1	Q15825-1

Frequencies

GnomAD3 genomes

AF:

0.00112

AC:

171

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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:

0.0113

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00133

AC:

335

AN:

251436

Hom.:

AF XY:

0.00120

AC XY:

163

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.0125

Gnomad NFE exome

AF:

0.000457

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000804

AC:

1176

AN:

1461820

Hom.:

Cov.:

AF XY:

0.000762

AC XY:

554

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.0106

Gnomad4 NFE exome

AF:

0.000508

Gnomad4 OTH exome

AF:

0.000447

GnomAD4 genome

AF:

0.00112

AC:

171

AN:

152306

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000577

Hom.:

Bravo

AF:

0.000261

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000865

AC:

105

EpiCase

AF:

0.000436

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Uncertain

0.68

D;.

Eigen

Benign

-0.030

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.071

MetaRNN

Benign

0.024

T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.5

M;M

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Pathogenic

-4.4

D;D

REVEL

Uncertain

0.40

Sift

Uncertain

0.011

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.72

P;.

Vest4

0.55

MVP

0.84

MPC

0.38

ClinPred

0.16

GERP RS

2.4

Varity_R

0.24

gMVP

0.65

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over