rs72648883

Positions:

• chr15-78619087-G-A
• chr15-78619087-G-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_000743.5(CHRNA3):​c.83-172C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000484 in 706,930 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00060 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00045 (0 hom.)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.848

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 Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000604 (92/152328) while in subpopulation AMR AF= 0.00163 (25/15306). AF 95% confidence interval is 0.00113. There are 0 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.83-172C>T		intron_variant		ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.83-172C>T		intron_variant			NP_001160166.1
CHRNA3	XM_006720382.4	c.-119-172C>T		intron_variant			XP_006720445.1
CHRNA3	NR_046313.2	n.285-172C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.83-172C>T		intron_variant		1	NM_000743.5	ENSP00000315602	P1

Frequencies

GnomAD3 genomes AF: 0.000604 AC: 92 AN: 152210 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.000957

GnomAD4 exome AF: 0.000451 AC: 250 AN: 554602 Hom.: 0 Cov.: 7 AF XY: 0.000423 AC XY: 122 AN XY: 288500

Gnomad4 AFR exome AF: 0.0000697

Gnomad4 AMR exome AF: 0.000792

Gnomad4 ASJ exome AF: 0.0000699

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000828

Gnomad4 FIN exome AF: 0.000875

Gnomad4 NFE exome AF: 0.000525

Gnomad4 OTH exome AF: 0.000373

GnomAD4 genome AF: 0.000604 AC: 92 AN: 152328 Hom.: 0 Cov.: 33 AF XY: 0.000510 AC XY: 38 AN XY: 74488

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000477 Hom.: 0

Bravo AF: 0.000714

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs72648883; hg19: chr15-78911429;