Variant chr2-174748545-A-T 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.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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CHRNA1	NM_000079.4 linkuse as main transcript	c.1242+35T>A	intron_variant	ENST00000348749.9
CHRNA1	NM_001039523.3 linkuse as main transcript	c.1317+35T>A	intron_variant
CHRNA1	XM_017003256.2 linkuse as main transcript	c.1338+35T>A	intron_variant
CHRNA1	XM_017003257.2 linkuse as main transcript	c.1263+35T>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA1	ENST00000348749.9 linkuse as main transcript	c.1242+35T>A		intron_variant		1	NM_000079.4	P1	P02708-2
	ENST00000442996.1 linkuse as main transcript	n.321+18721A>T		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes

AF:

0.0188

AC:

4663

AN:

248230

Hom.:

147

AF XY:

0.0176

AC XY:

2367

AN XY:

134204

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 SAS exome

AF:

0.0222

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

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.0126

Gnomad4 ASJ exome

AF:

0.0123

Gnomad4 EAS exome

AF:

0.0636

Gnomad4 SAS exome

AF:

0.0231

Gnomad4 FIN exome

AF:

0.000470

Gnomad4 NFE exome

AF:

0.00554

Gnomad4 OTH exome

AF:

0.0160

GnomAD4 genome

AF:

0.0381

AC:

5800

AN:

152146

Hom.:

277

Cov.:

AF XY:

0.0376

AC XY:

2798

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.0202

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.0506

Gnomad4 SAS

AF:

0.0208

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00547

Gnomad4 OTH

AF:

0.0403

Alfa

AF:

0.0219

Hom.:

Bravo

AF:

0.0441

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Aug 14, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.97

DANN

Benign

0.69

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