rs2229957

Positions:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_000079.4(CHRNA1):c.960C>T(p.His320=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0732 in 1,613,996 control chromosomes in the GnomAD database, including 5,798 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 827 hom., cov: 32)

Exomes 𝑓: 0.071 ( 4971 hom. )

Consequence

CHRNA1
NM_000079.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 4.79

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 2-174749988-G-A is Benign according to our data. Variant chr2-174749988-G-A is described in ClinVar as [Benign]. Clinvar id is 128735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-174749988-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CHRNA1	NM_000079.4 linkuse as main transcript	c.960C>T	p.His320=	synonymous_variant	7/9	ENST00000348749.9	NP_000070.1
CHRNA1	NM_001039523.3 linkuse as main transcript	c.1035C>T	p.His345=	synonymous_variant	8/10		NP_001034612.1
CHRNA1	XM_017003256.2 linkuse as main transcript	c.1056C>T	p.His352=	synonymous_variant	7/9		XP_016858745.1
CHRNA1	XM_017003257.2 linkuse as main transcript	c.981C>T	p.His327=	synonymous_variant	6/8		XP_016858746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA1	ENST00000348749.9 linkuse as main transcript	c.960C>T	p.His320=	synonymous_variant	7/9	1	NM_000079.4	ENSP00000261008	P1	P02708-2
	ENST00000442996.1 linkuse as main transcript	n.321+20164G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.0914

AC:

13892

AN:

152038

Hom.:

820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.0570

Gnomad AMR

AF:

0.0640

Gnomad ASJ

AF:

0.0683

Gnomad EAS

AF:

0.0613

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.0223

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.0662

Gnomad OTH

AF:

0.0880

GnomAD3 exomes

AF:

0.0808

AC:

20297

AN:

251154

Hom.:

1209

AF XY:

0.0863

AC XY:

11719

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.157

Gnomad AMR exome

AF:

0.0446

Gnomad ASJ exome

AF:

0.0693

Gnomad EAS exome

AF:

0.0539

Gnomad SAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.0218

Gnomad NFE exome

AF:

0.0653

Gnomad OTH exome

AF:

0.0827

GnomAD4 exome

AF:

0.0713

AC:

104276

AN:

1461840

Hom.:

4971

Cov.:

AF XY:

0.0751

AC XY:

54650

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.0469

Gnomad4 ASJ exome

AF:

0.0667

Gnomad4 EAS exome

AF:

0.0558

Gnomad4 SAS exome

AF:

0.197

Gnomad4 FIN exome

AF:

0.0246

Gnomad4 NFE exome

AF:

0.0620

Gnomad4 OTH exome

AF:

0.0810

GnomAD4 genome

AF:

0.0915

AC:

13925

AN:

152156

Hom.:

827

Cov.:

AF XY:

0.0916

AC XY:

6815

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.0639

Gnomad4 ASJ

AF:

0.0683

Gnomad4 EAS

AF:

0.0611

Gnomad4 SAS

AF:

0.210

Gnomad4 FIN

AF:

0.0223

Gnomad4 NFE

AF:

0.0662

Gnomad4 OTH

AF:

0.0946

Alfa

AF:

0.0708

Hom.:

700

Bravo

AF:

0.0933

Asia WGS

AF:

0.172

AC:

595

AN:

3478

EpiCase

AF:

0.0706

EpiControl

AF:

0.0701

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2016	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. -

Lethal multiple pterygium syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Congenital myasthenic syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.88

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