15-78615003-C-T

Variant names:

• chr15-78615003-C-T
• rs2869546
• NM_000743.5:c.377+2021G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000743.5(CHRNA3):​c.377+2021G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 151,900 control chromosomes in the GnomAD database, including 32,131 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 0.65 (32131 hom., cov: 30)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.791 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.377+2021G>A		intron_variant	Intron 4 of 5	ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.377+2021G>A		intron_variant	Intron 4 of 5		NP_001160166.1
CHRNA3	XM_006720382.4	c.176+2021G>A		intron_variant	Intron 4 of 5		XP_006720445.1
CHRNA3	NR_046313.2	n.579+2021G>A		intron_variant	Intron 4 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.377+2021G>A		intron_variant	Intron 4 of 5	1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.377+2021G>A		intron_variant	Intron 4 of 5	1		ENSP00000267951.4
CHRNA3	ENST00000559658.5	n.377+2021G>A		intron_variant	Intron 4 of 7	2		ENSP00000452896.1

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98268 AN: 151782 Hom.: 32088 Cov.: 30

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.666

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.648 AC: 98368 AN: 151900 Hom.: 32131 Cov.: 30 AF XY: 0.650 AC XY: 48275 AN XY: 74246

Gnomad4 AFR AF: 0.625

Gnomad4 AMR AF: 0.755

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.670

Alfa AF: 0.617 Hom.: 8586

Bravo AF: 0.655

Asia WGS AF: 0.732 AC: 2546 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.49

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

Other links and lift over

dbSNP: rs2869546; hg19: chr15-78907345;