Variant chr2-174758060-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000079.4(CHRNA1):c.235-385C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,613,942 control chromosomes in the GnomAD database, including 806,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 1.0 ( 75802 hom., cov: 32)

Exomes 𝑓: 1.0 ( 730412 hom. )

Consequence

CHRNA1
NM_000079.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.00800

Variant links:

Genes affected

CHRNA1 (HGNC:1955): (cholinergic receptor nicotinic alpha 1 subunit) The muscle acetylcholine receptor consiststs of 5 subunits of 4 different types: 2 alpha subunits and 1 each of the beta, gamma, and delta subunits. This gene encodes an alpha subunit that plays a role in acetlycholine binding/channel gating. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Nov 2012]

CHRNA1 links:

ENSG00000236449 (HGNC:):

ENSG00000236449 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-174758060-G-A is Benign according to our data. Variant chr2-174758060-G-A is described in ClinVar as [Benign]. Clinvar id is 257237.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CHRNA1	NM_000079.4 linkuse as main transcript	c.235-385C>T	intron_variant	ENST00000348749.9	NP_000070.1	P02708-2Q53SH4
CHRNA1	NM_001039523.3 linkuse as main transcript	c.235-40C>T	intron_variant		NP_001034612.1	P02708-1Q53SH4
CHRNA1	XM_017003256.2 linkuse as main transcript	c.256-40C>T	intron_variant		XP_016858745.1
CHRNA1	XM_017003257.2 linkuse as main transcript	c.256-385C>T	intron_variant		XP_016858746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA1	ENST00000348749.9 linkuse as main transcript	c.235-385C>T		intron_variant		1	NM_000079.4	ENSP00000261008.5		P02708-2

Frequencies

GnomAD3 genomes

AF:

0.998

AC:

151855

AN:

152226

Hom.:

75743

Cov.:

show subpopulations

Gnomad AFR

AF:

0.992

Gnomad AMI

AF:

0.997

Gnomad AMR

AF:

0.999

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

1.00

GnomAD3 exomes

AF:

0.999

AC:

248515

AN:

248648

Hom.:

124192

AF XY:

1.00

AC XY:

134622

AN XY:

134674

show subpopulations

Gnomad AFR exome

AF:

0.993

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1461206

AN:

1461598

Hom.:

730412

Cov.:

AF XY:

1.00

AC XY:

726939

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.990

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.999

GnomAD4 genome

AF:

0.998

AC:

151973

AN:

152344

Hom.:

75802

Cov.:

AF XY:

0.998

AC XY:

74324

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.992

Gnomad4 AMR

AF:

0.999

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

1.00

Alfa

AF:

0.999

Hom.:

13177

Bravo

AF:

0.997

Asia WGS

AF:

1.00

AC:

3477

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Myasthenic syndrome, congenital, 1B, fast-channel

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Lethal multiple pterygium syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Congenital myasthenic syndrome 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.9

DANN

Benign

0.87

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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