Variant 15-78617110-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000743.5(CHRNA3):c.291A>G(p.Lys97Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 1,610,160 control chromosomes in the GnomAD database, including 323,844 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.62 ( 30013 hom., cov: 32)

Exomes 𝑓: 0.63 ( 293831 hom. )

Consequence

CHRNA3
NM_000743.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.731

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:

CHRNA3 (HGNC:):

CHRNA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 15-78617110-T-C is Benign according to our data. Variant chr15-78617110-T-C is described in ClinVar as [Benign]. Clinvar id is 1209767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.731 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA3	NM_000743.5 linkuse as main transcript	c.291A>G	p.Lys97Lys	synonymous_variant	4/6	ENST00000326828.6	NP_000734.2	P32297-2
CHRNA3	NM_001166694.2 linkuse as main transcript	c.291A>G	p.Lys97Lys	synonymous_variant	4/6		NP_001160166.1	P32297-3
CHRNA3	XM_006720382.4 linkuse as main transcript	c.90A>G	p.Lys30Lys	synonymous_variant	4/6		XP_006720445.1
CHRNA3	NR_046313.2 linkuse as main transcript	n.493A>G		non_coding_transcript_exon_variant	4/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CHRNA3	ENST00000326828.6 linkuse as main transcript	c.291A>G	p.Lys97Lys	synonymous_variant	4/6	1	NM_000743.5	ENSP00000315602.5	P32297-2
CHRNA3	ENST00000348639.7 linkuse as main transcript	c.291A>G	p.Lys97Lys	synonymous_variant	4/6	1		ENSP00000267951.4	P32297-3
CHRNA3	ENST00000559658.5 linkuse as main transcript	n.291A>G		non_coding_transcript_exon_variant	4/8	2		ENSP00000452896.1	P32297-2

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

94868

AN:

151894

Hom.:

29976

Cov.:

show subpopulations

Gnomad AFR

AF:

0.561

Gnomad AMI

AF:

0.594

Gnomad AMR

AF:

0.752

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.561

Gnomad SAS

AF:

0.675

Gnomad FIN

AF:

0.650

Gnomad MID

AF:

0.793

Gnomad NFE

AF:

0.630

Gnomad OTH

AF:

0.654

GnomAD3 exomes

AF:

0.662

AC:

165601

AN:

250308

Hom.:

55733

AF XY:

0.661

AC XY:

89387

AN XY:

135236

show subpopulations

Gnomad AFR exome

AF:

0.566

Gnomad AMR exome

AF:

0.838

Gnomad ASJ exome

AF:

0.656

Gnomad EAS exome

AF:

0.562

Gnomad SAS exome

AF:

0.696

Gnomad FIN exome

AF:

0.659

Gnomad NFE exome

AF:

0.629

Gnomad OTH exome

AF:

0.661

GnomAD4 exome

AF:

0.632

AC:

922035

AN:

1458148

Hom.:

293831

Cov.:

AF XY:

0.633

AC XY:

459598

AN XY:

725526

show subpopulations

Gnomad4 AFR exome

AF:

0.569

Gnomad4 AMR exome

AF:

0.828

Gnomad4 ASJ exome

AF:

0.642

Gnomad4 EAS exome

AF:

0.577

Gnomad4 SAS exome

AF:

0.687

Gnomad4 FIN exome

AF:

0.655

Gnomad4 NFE exome

AF:

0.622

Gnomad4 OTH exome

AF:

0.632

GnomAD4 genome

AF:

0.625

AC:

94953

AN:

152012

Hom.:

30013

Cov.:

AF XY:

0.626

AC XY:

46528

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.561

Gnomad4 AMR

AF:

0.753

Gnomad4 ASJ

AF:

0.638

Gnomad4 EAS

AF:

0.561

Gnomad4 SAS

AF:

0.676

Gnomad4 FIN

AF:

0.650

Gnomad4 NFE

AF:

0.630

Gnomad4 OTH

AF:

0.659

Alfa

AF:

0.623

Hom.:

22309

Bravo

AF:

0.628

Asia WGS

AF:

0.642

AC:

2233

AN:

3478

EpiCase

AF:

0.648

EpiControl

AF:

0.642

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

Urinary bladder, atony of

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.3

DANN

Benign

0.67

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