rs6495308

Positions:

• chr15-78615314-T-C
• chr15-78615314-T-G

Variant summary

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

The NM_000743.5(CHRNA3):​c.377+1710A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 151,980 control chromosomes in the GnomAD database, including 8,056 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 0.30 (8056 hom., cov: 32)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314

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 = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.377+1710A>G		intron_variant		ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.377+1710A>G		intron_variant			NP_001160166.1
CHRNA3	XM_006720382.4	c.176+1710A>G		intron_variant			XP_006720445.1
CHRNA3	NR_046313.2	n.579+1710A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.377+1710A>G		intron_variant		1	NM_000743.5	ENSP00000315602	P1
CHRNA3	ENST00000348639.7	c.377+1710A>G		intron_variant		1		ENSP00000267951
CHRNA3	ENST00000559658.5	c.377+1710A>G		intron_variant, NMD_transcript_variant		2		ENSP00000452896

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45709 AN: 151862 Hom.: 8030 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.301 AC: 45776 AN: 151980 Hom.: 8056 Cov.: 32 AF XY: 0.309 AC XY: 22990 AN XY: 74304

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.478

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.307

Alfa AF: 0.252 Hom.: 5923

Bravo AF: 0.316

Asia WGS AF: 0.571 AC: 1984 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	1.8
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs6495308; hg19: chr15-78907656;