Variant rs71581741 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000326828.6(CHRNA3):c.377+8G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,604,428 control chromosomes in the GnomAD database, including 790 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.040 ( 367 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 423 hom. )

Consequence

CHRNA3
ENST00000326828.6 splice_region, intron

Scores

Splicing: ADA: 0.0003934

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0360

Variant links:

Genes affected

CHRNA3 (HGNC:1957): (cholinergic receptor nicotinic alpha 3 subunit) This locus encodes a member of the nicotinic acetylcholine receptor family of proteins. Members of this family of proteins form pentameric complexes comprised of both alpha and beta subunits. This locus encodes an alpha-type subunit, as it contains characteristic adjacent cysteine residues. The encoded protein is a ligand-gated ion channel that likely plays a role in neurotransmission. Polymorphisms in this gene have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]

CHRNA3 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=-0.71).

BP6

Variant 15-78617016-C-G is Benign according to our data. Variant chr15-78617016-C-G is described in ClinVar as [Benign]. Clinvar id is 2039314.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CHRNA3	NM_000743.5 linkuse as main transcript	c.377+8G>C	splice_region_variant, intron_variant	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2 linkuse as main transcript	c.377+8G>C	splice_region_variant, intron_variant		NP_001160166.1
CHRNA3	XM_006720382.4 linkuse as main transcript	c.176+8G>C	splice_region_variant, intron_variant		XP_006720445.1
CHRNA3	NR_046313.2 linkuse as main transcript	n.579+8G>C	splice_region_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6 linkuse as main transcript	c.377+8G>C	splice_region_variant, intron_variant	1	NM_000743.5	ENSP00000315602	P1	P32297-2
CHRNA3	ENST00000348639.7 linkuse as main transcript	c.377+8G>C	splice_region_variant, intron_variant	1		ENSP00000267951		P32297-3
CHRNA3	ENST00000559658.5 linkuse as main transcript	c.377+8G>C	splice_region_variant, intron_variant, NMD_transcript_variant	2		ENSP00000452896		P32297-2

Frequencies

GnomAD3 genomes

AF:

0.0399

AC:

6072

AN:

152202

Hom.:

367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0149

Gnomad ASJ

AF:

0.0233

Gnomad EAS

AF:

0.0668

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00184

Gnomad OTH

AF:

0.0320

GnomAD3 exomes

AF:

0.0168

AC:

4156

AN:

247692

Hom.:

194

AF XY:

0.0142

AC XY:

1904

AN XY:

133828

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.00712

Gnomad ASJ exome

AF:

0.0196

Gnomad EAS exome

AF:

0.0729

Gnomad SAS exome

AF:

0.00167

Gnomad FIN exome

AF:

0.0000946

Gnomad NFE exome

AF:

0.00190

Gnomad OTH exome

AF:

0.00972

GnomAD4 exome

AF:

0.00743

AC:

10786

AN:

1452108

Hom.:

423

Cov.:

AF XY:

0.00680

AC XY:

4911

AN XY:

722626

show subpopulations

Gnomad4 AFR exome

AF:

0.132

Gnomad4 AMR exome

AF:

0.00770

Gnomad4 ASJ exome

AF:

0.0213

Gnomad4 EAS exome

AF:

0.0660

Gnomad4 SAS exome

AF:

0.00192

Gnomad4 FIN exome

AF:

0.0000377

Gnomad4 NFE exome

AF:

0.00158

Gnomad4 OTH exome

AF:

0.0153

GnomAD4 genome

AF:

0.0399

AC:

6077

AN:

152320

Hom.:

367

Cov.:

AF XY:

0.0396

AC XY:

2950

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.0149

Gnomad4 ASJ

AF:

0.0233

Gnomad4 EAS

AF:

0.0666

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00184

Gnomad4 OTH

AF:

0.0317

Alfa

AF:

0.0159

Hom.:

Bravo

AF:

0.0449

Asia WGS

AF:

0.0330

AC:

114

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.6

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00039

dbscSNV1_RF

Benign

0.016

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