Variant rs12899226 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000745.4(CHRNA5):c.*1843T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.033 in 158,372 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.032 ( 111 hom., cov: 32)

Exomes 𝑓: 0.058 ( 14 hom. )

Consequence

CHRNA5
NM_000745.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.504

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:

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0556 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4 linkuse as main transcript	c.*1843T>G		3_prime_UTR_variant	6/6	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9 linkuse as main transcript	c.*1843T>G	3_prime_UTR_variant	6/6	1	NM_000745.4	ENSP00000299565	P1
CHRNA3	ENST00000348639.7 linkuse as main transcript	c.1390-1905A>C	intron_variant		1		ENSP00000267951		P32297-3
CHRNA3	ENST00000559002.5 linkuse as main transcript	n.193+1444A>C	intron_variant, non_coding_transcript_variant		1
CHRNA3	ENST00000559658.5 linkuse as main transcript	c.*65-1085A>C	intron_variant, NMD_transcript_variant		2		ENSP00000452896		P32297-2

Frequencies

GnomAD3 genomes

AF:

0.0320

AC:

4865

AN:

152142

Hom.:

111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0122

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0240

Gnomad ASJ

AF:

0.0208

Gnomad EAS

AF:

0.00868

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.0261

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0504

Gnomad OTH

AF:

0.0301

GnomAD4 exome

AF:

0.0578

AC:

353

AN:

6112

Hom.:

Cov.:

AF XY:

0.0602

AC XY:

180

AN XY:

2988

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0149

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0609

Gnomad4 OTH exome

AF:

0.0439

GnomAD4 genome

AF:

0.0320

AC:

4866

AN:

152260

Hom.:

111

Cov.:

AF XY:

0.0305

AC XY:

2272

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.0240

Gnomad4 ASJ

AF:

0.0208

Gnomad4 EAS

AF:

0.00870

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.0261

Gnomad4 NFE

AF:

0.0504

Gnomad4 OTH

AF:

0.0293

Alfa

AF:

0.0367

Hom.:

Bravo

AF:

0.0310

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.2

DANN

Benign

0.50

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over