Variant rs17838546 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000079.4(CHRNA1):c.1243-38C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,612,898 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.011 ( 16 hom., cov: 32)

Exomes 𝑓: 0.015 ( 225 hom. )

Consequence

CHRNA1
NM_000079.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.59

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 2-174748293-G-A is Benign according to our data. Variant chr2-174748293-G-A is described in ClinVar as [Benign]. Clinvar id is 257233.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0108 (1645/152306) while in subpopulation NFE AF= 0.0154 (1048/68042). AF 95% confidence interval is 0.0146. There are 16 homozygotes in gnomad4. There are 800 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 16 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
CHRNA1	NM_000079.4 linkuse as main transcript	c.1243-38C>T	intron_variant	ENST00000348749.9	NP_000070.1	P02708-2Q53SH4
CHRNA1	NM_001039523.3 linkuse as main transcript	c.1318-38C>T	intron_variant		NP_001034612.1	P02708-1Q53SH4
CHRNA1	XM_017003256.2 linkuse as main transcript	c.1339-38C>T	intron_variant		XP_016858745.1
CHRNA1	XM_017003257.2 linkuse as main transcript	c.1264-38C>T	intron_variant		XP_016858746.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA1	ENST00000348749.9 linkuse as main transcript	c.1243-38C>T		intron_variant		1	NM_000079.4	ENSP00000261008.5		P02708-2

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1645

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00364

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00713

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.0222

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.0154

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.0109

AC:

2713

AN:

249274

Hom.:

AF XY:

0.0108

AC XY:

1460

AN XY:

134946

show subpopulations

Gnomad AFR exome

AF:

0.00267

Gnomad AMR exome

AF:

0.00519

Gnomad ASJ exome

AF:

0.0151

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00327

Gnomad FIN exome

AF:

0.0211

Gnomad NFE exome

AF:

0.0151

Gnomad OTH exome

AF:

0.0143

GnomAD4 exome

AF:

0.0154

AC:

22528

AN:

1460592

Hom.:

225

Cov.:

AF XY:

0.0149

AC XY:

10839

AN XY:

726622

show subpopulations

Gnomad4 AFR exome

AF:

0.00236

Gnomad4 AMR exome

AF:

0.00510

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00302

Gnomad4 FIN exome

AF:

0.0217

Gnomad4 NFE exome

AF:

0.0175

Gnomad4 OTH exome

AF:

0.0154

GnomAD4 genome

AF:

0.0108

AC:

1645

AN:

152306

Hom.:

Cov.:

AF XY:

0.0107

AC XY:

800

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00363

Gnomad4 AMR

AF:

0.00713

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00353

Gnomad4 FIN

AF:

0.0222

Gnomad4 NFE

AF:

0.0154

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.0130

Hom.:

Bravo

AF:

0.00933

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

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

-0.57

CADD

Benign

DANN

Benign

0.85

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