rs2305415

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000079.4(CHRNA1):c.1242+35T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,606,846 control chromosomes in the GnomAD database, including 704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 277 hom., cov: 33)

Exomes 𝑓: 0.011 ( 427 hom. )

Consequence

CHRNA1
NM_000079.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.00700

Publications

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

CHRNA1 links:

ENSG00000236449 (HGNC:):

ENSG00000236449 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_000079.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

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

BP6

Variant 2-174748545-A-T is Benign according to our data. Variant chr2-174748545-A-T is described in ClinVar as Benign. ClinVar VariationId is 257232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000079.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA1	NM_000079.4	MANE Select	c.1242+35T>A		intron	N/A	NP_000070.1	Q53SH4
	CHRNA1	NM_001039523.3		c.1317+35T>A		intron	N/A	NP_001034612.1	P02708-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHRNA1	ENST00000348749.9	TSL:1 MANE Select	c.1242+35T>A	intron	N/A	ENSP00000261008.5	P02708-2
ENSG00000236449	ENST00000442996.1	TSL:1	n.321+18721A>T	intron	N/A
CHRNA1	ENST00000261007.9	TSL:2	c.1317+35T>A	intron	N/A	ENSP00000261007.5	P02708-1

Frequencies

GnomAD3 genomes

AF:

0.0381

AC:

5789

AN:

152028

Hom.:

276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.112

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0202

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.0504

Gnomad SAS

AF:

0.0212

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00547

Gnomad OTH

AF:

0.0384

GnomAD2 exomes

AF:

0.0188

AC:

4663

AN:

248230

AF XY:

0.0176

show subpopulations

Gnomad AFR exome

AF:

0.116

Gnomad AMR exome

AF:

0.0113

Gnomad ASJ exome

AF:

0.0127

Gnomad EAS exome

AF:

0.0458

Gnomad FIN exome

AF:

0.000421

Gnomad NFE exome

AF:

0.00612

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0113

AC:

16466

AN:

1454700

Hom.:

427

Cov.:

AF XY:

0.0115

AC XY:

8327

AN XY:

722350

show subpopulations

African (AFR)

AF:

0.115

AC:

3806

AN:

33206

American (AMR)

AF:

0.0126

AC:

556

AN:

44150

Ashkenazi Jewish (ASJ)

AF:

0.0123

AC:

320

AN:

25938

East Asian (EAS)

AF:

0.0636

AC:

2513

AN:

39494

South Asian (SAS)

AF:

0.0231

AC:

1981

AN:

85866

European-Finnish (FIN)

AF:

0.000470

AC:

AN:

53188

Middle Eastern (MID)

AF:

0.0298

AC:

171

AN:

5734

European-Non Finnish (NFE)

AF:

0.00554

AC:

6133

AN:

1107084

Other (OTH)

AF:

0.0160

AC:

961

AN:

60040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

836

1672

2507

3343

4179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

362

724

1086

1448

1810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0381

AC:

5800

AN:

152146

Hom.:

277

Cov.:

AF XY:

0.0376

AC XY:

2798

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.111

AC:

4624

AN:

41472

American (AMR)

AF:

0.0202

AC:

309

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0115

AC:

AN:

3470

East Asian (EAS)

AF:

0.0506

AC:

262

AN:

5182

South Asian (SAS)

AF:

0.0208

AC:

100

AN:

4816

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00547

AC:

372

AN:

67998

Other (OTH)

AF:

0.0403

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

270

541

811

1082

1352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0219

Hom.:

Bravo

AF:

0.0441

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.97

(source)

DANN

Benign

0.69

PhyloP100

-0.0070

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over