chr15-78616885-T-G

Position:

• chr15-78616885-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000743.5(CHRNA3):​c.377+139A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000445 in 604,832 control chromosomes in the GnomAD database, including 2 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 0.00030 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00049 (2 hom.)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.990

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]

CHRNA3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000302 (46/152278) while in subpopulation SAS AF= 0.000829 (4/4828). AF 95% confidence interval is 0.000368. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.377+139A>C		intron_variant		ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.377+139A>C		intron_variant			NP_001160166.1
CHRNA3	XM_006720382.4	c.176+139A>C		intron_variant			XP_006720445.1
CHRNA3	NR_046313.2	n.579+139A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.377+139A>C		intron_variant		1	NM_000743.5	ENSP00000315602.5
CHRNA3	ENST00000348639.7	c.377+139A>C		intron_variant		1		ENSP00000267951.4
CHRNA3	ENST00000559658.5	n.377+139A>C		intron_variant		2		ENSP00000452896.1

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 46 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.000493 AC: 223 AN: 452554 Hom.: 2 AF XY: 0.000533 AC XY: 127 AN XY: 238410

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000542

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00212

Gnomad4 FIN exome AF: 0.0000982

Gnomad4 NFE exome AF: 0.000409

Gnomad4 OTH exome AF: 0.000384

GnomAD4 genome AF: 0.000302 AC: 46 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74452

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000109 Hom.: 0

Bravo AF: 0.000242

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.16
DANN	Benign	0.31

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: rs3743076; hg19: chr15-78909227;