Variant 15-78565773-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000745.4(CHRNA5):c.54G>A(p.Gln18=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000314 in 1,218,754 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00052 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00029 ( 2 hom. )

Consequence

CHRNA5
NM_000745.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

CHRNA5 (HGNC:1959): (cholinergic receptor nicotinic alpha 5 subunit) The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are thought to be heteropentamers composed of separate but similar subunits. Defects in this gene have been linked to susceptibility to lung cancer type 2 (LNCR2).[provided by RefSeq, Jun 2010]

CHRNA5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BP6

Variant 15-78565773-G-A is Benign according to our data. Variant chr15-78565773-G-A is described in ClinVar as [Benign]. Clinvar id is 732206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.19 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4 linkuse as main transcript	c.54G>A	p.Gln18=	synonymous_variant	1/6	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9 linkuse as main transcript	c.54G>A	p.Gln18=	synonymous_variant	1/6	1	NM_000745.4	ENSP00000299565	P1
CHRNA5	ENST00000559554.5 linkuse as main transcript	c.54G>A	p.Gln18=	synonymous_variant	1/6	3		ENSP00000453519

Frequencies

GnomAD3 genomes

AF:

0.000523

AC:

AN:

151166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000286

AC:

305

AN:

1067478

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

142

AN XY:

504046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0105

Gnomad4 SAS exome

AF:

0.000206

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000110

Gnomad4 OTH exome

AF:

0.000726

GnomAD4 genome

AF:

0.000516

AC:

AN:

151276

Hom.:

Cov.:

AF XY:

0.000541

AC XY:

AN XY:

73934

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000658

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0151

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000654

Asia WGS

AF:

0.00261

AC:

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

9.8

DANN

Benign

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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