rs1051730

chr15-78601997-G-A

Variant summary

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

The NM_000743(CHRNA3):c.645C>T(p.Tyr215=) variant causes a synonymous change. The variant allele was found at a frequency of 0.258 in 151744 control chromosomes in the gnomAD Genomes database, including 6060 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.26 ( 6060 hom., cov: 31)

Exomes 𝑓: 0.27 ( 10777 hom. )

Consequence

CHRNA3
NM_000743 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:2

Conservation

PhyloP100: 5.50

Links

CHRNA3 (HGNC:1957):

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 15:78601997-G>A is Benign according to our data. Variant chr15-78601997-G-A is described in ClinVar as [Benign]. Clinvar id is 17503. Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CHRNA3	NM_000743.5 linkuse as main transcript	c.645C>T	p.Tyr215=	synonymous_variant	5/6	ENST00000326828.6
CHRNA3	NM_001166694.2 linkuse as main transcript	c.645C>T	p.Tyr215=	synonymous_variant	5/6
CHRNA3	XM_006720382.4 linkuse as main transcript	c.444C>T	p.Tyr148=	synonymous_variant	5/6
CHRNA3	NR_046313.2 linkuse as main transcript	n.847C>T		non_coding_transcript_exon_variant	5/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA3	ENST00000326828.6 linkuse as main transcript	c.645C>T	p.Tyr215=	synonymous_variant	5/6	1	NM_000743.5	P1	P32297-2
CHRNA3	ENST00000348639.7 linkuse as main transcript	c.645C>T	p.Tyr215=	synonymous_variant	5/6	1			P32297-3
CHRNA3	ENST00000558903.1 linkuse as main transcript	n.352C>T		non_coding_transcript_exon_variant	2/2	4
CHRNA3	ENST00000559658.5 linkuse as main transcript	c.645C>T	p.Tyr215=	synonymous_variant, NMD_transcript_variant	5/8	2			P32297-2

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39177

AN:

151744

Hom.:

6060

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.234

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.0320

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.269

AC:

67652

AN:

251254

Hom.:

10777

AF XY:

0.279

AC XY:

37940

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.166

Gnomad ASJ exome

AF:

0.383

Gnomad EAS exome

AF:

0.0322

Gnomad SAS exome

AF:

0.236

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.349

Gnomad OTH exome

AF:

0.299

GnomAD4 exome

AF:

0.310

AC:

453238

AN:

1461244

Hom.:

74434

AF XY:

0.310

AC XY:

225164

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.176

Gnomad4 ASJ exome

AF:

0.382

Gnomad4 EAS exome

AF:

0.0265

Gnomad4 SAS exome

AF:

0.239

Gnomad4 FIN exome

AF:

0.330

Gnomad4 NFE exome

AF:

0.335

Gnomad4 OTH exome

AF:

0.295

Alfa

AF:

0.324

Hom.:

15344

Bravo

AF:

0.244

Asia WGS

AF:

0.117

AC:

412

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 03, 2022

- -

Lung cancer susceptibility 2

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2008

- -

Smoking as a quantitative trait locus 3

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2008

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

Cadd

Benign

8.6

Dann

Benign

0.56

Splicing

Find out SpliceAI 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

Links

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over