Genetic Variant CHRNA1:c.43+59G>T (chr2-174764293-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000079.4(CHRNA1):c.43+59G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,553,240 control chromosomes in the GnomAD database, including 161,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 11733 hom., cov: 32)

Exomes 𝑓: 0.45 ( 149550 hom. )

Consequence

CHRNA1
NM_000079.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.779

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=-0.83).

BP6

Variant 2-174764293-C-A is Benign according to our data. Variant chr2-174764293-C-A is described in ClinVar as [Benign]. Clinvar id is 680121.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-174764293-C-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA1	NM_000079.4 link	c.43+59G>T		intron_variant	Intron 1 of 8	ENST00000348749.9	NP_000070.1	P02708-2Q53SH4
CHRNA1	NM_001039523.3 link	c.43+59G>T		intron_variant	Intron 1 of 9		NP_001034612.1	P02708-1Q53SH4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA1	ENST00000348749.9 link	c.43+59G>T		intron_variant	Intron 1 of 8	1	NM_000079.4	ENSP00000261008.5		P02708-2

Frequencies

GnomAD3 genomes

AF:

0.360

AC:

54647

AN:

151930

Hom.:

11737

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.432

Gnomad ASJ

AF:

0.531

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.252

Gnomad FIN

AF:

0.477

Gnomad MID

AF:

0.423

Gnomad NFE

AF:

0.477

Gnomad OTH

AF:

0.410

GnomAD4 exome

AF:

0.453

AC:

634385

AN:

1401190

Hom.:

149550

AF XY:

0.448

AC XY:

312271

AN XY:

696458

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.410

Gnomad4 ASJ exome

AF:

0.544

Gnomad4 EAS exome

AF:

0.216

Gnomad4 SAS exome

AF:

0.266

Gnomad4 FIN exome

AF:

0.481

Gnomad4 NFE exome

AF:

0.485

Gnomad4 OTH exome

AF:

0.437

GnomAD4 genome

AF:

0.359

AC:

54657

AN:

152050

Hom.:

11733

Cov.:

AF XY:

0.356

AC XY:

26440

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.123

Gnomad4 AMR

AF:

0.432

Gnomad4 ASJ

AF:

0.531

Gnomad4 EAS

AF:

0.205

Gnomad4 SAS

AF:

0.251

Gnomad4 FIN

AF:

0.477

Gnomad4 NFE

AF:

0.477

Gnomad4 OTH

AF:

0.407

Alfa

AF:

0.459

Hom.:

10722

Bravo

AF:

0.349

Asia WGS

AF:

0.221

AC:

771

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Myasthenic syndrome, congenital, 1B, fast-channel

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Lethal multiple pterygium syndrome

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Congenital myasthenic syndrome 1A

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.90

DANN

Benign

0.70

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