dbSNP rs1376866: CHRNA1:c.43+1224G>A (chr2-174763128-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000079.4(CHRNA1):c.43+1224G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,082 control chromosomes in the GnomAD database, including 45,490 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.75 ( 45490 hom., cov: 32)

Consequence

CHRNA1
NM_000079.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0230

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 1A
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
lethal multiple pterygium syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
myasthenic syndrome, congenital, 1B, fast-channel
Inheritance: AR, AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHRNA1 links:

ENSG00000236449 (HGNC:):

ENSG00000236449 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA1	NM_000079.4 link	c.43+1224G>A		intron_variant	Intron 1 of 8	ENST00000348749.9	NP_000070.1
CHRNA1	NM_001039523.3 link	c.43+1224G>A		intron_variant	Intron 1 of 9		NP_001034612.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA1	ENST00000348749.9 link	c.43+1224G>A		intron_variant	Intron 1 of 8	1	NM_000079.4	ENSP00000261008.5

Frequencies

GnomAD3 genomes

AF:

0.747

AC:

113523

AN:

151964

Hom.:

45494

Cov.:

show subpopulations

Gnomad AFR

AF:

0.427

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.859

Gnomad ASJ

AF:

0.832

Gnomad EAS

AF:

0.931

Gnomad SAS

AF:

0.721

Gnomad FIN

AF:

0.932

Gnomad MID

AF:

0.794

Gnomad NFE

AF:

0.869

Gnomad OTH

AF:

0.768

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.747

AC:

113545

AN:

152082

Hom.:

45490

Cov.:

AF XY:

0.752

AC XY:

55905

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.427

AC:

17680

AN:

41440

American (AMR)

AF:

0.859

AC:

13118

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.832

AC:

2888

AN:

3472

East Asian (EAS)

AF:

0.931

AC:

4820

AN:

5176

South Asian (SAS)

AF:

0.720

AC:

3461

AN:

4804

European-Finnish (FIN)

AF:

0.932

AC:

9876

AN:

10600

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.869

AC:

59071

AN:

67996

Other (OTH)

AF:

0.761

AC:

1607

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1201

2402

3602

4803

6004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

822

1644

2466

3288

4110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.837

Hom.:

39936

Bravo

AF:

0.730

Asia WGS

AF:

0.761

AC:

2648

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

(source)

DANN

Benign

0.48

PhyloP100

-0.023

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over