rs11637630

Positions:

• chr15-78607377-G-A
• chr15-78607377-G-C
• chr15-78607377-G-T

Variant summary

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

The NM_000743.5(CHRNA3):​c.378-5113C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,010 control chromosomes in the GnomAD database, including 38,864 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 0.71 (38858 hom., cov: 31)
  • Exomes 𝑓: 0.67 (6 hom.)
• Consequence: CHRNA3 NM_000743.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.666

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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA3	NM_000743.5	c.378-5113C>T		intron_variant		ENST00000326828.6	NP_000734.2
CHRNA3	NM_001166694.2	c.378-5113C>T		intron_variant			NP_001160166.1
CHRNA3	XM_006720382.4	c.177-5113C>T		intron_variant			XP_006720445.1
CHRNA3	NR_046313.2	n.580-5113C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA3	ENST00000326828.6	c.378-5113C>T		intron_variant		1	NM_000743.5	ENSP00000315602	P1
CHRNA3	ENST00000348639.7	c.378-5113C>T		intron_variant		1		ENSP00000267951
CHRNA3	ENST00000559658.5	c.378-5113C>T		intron_variant, NMD_transcript_variant		2		ENSP00000452896
CHRNA3	ENST00000558903.1	n.84+64C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107516 AN: 151868 Hom.: 38838 Cov.: 31

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.536

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.703

GnomAD4 exome AF: 0.667 AC: 16 AN: 24 Hom.: 6 AF XY: 0.600 AC XY: 12 AN XY: 20

Gnomad4 AFR exome AF: 0.500

Gnomad4 NFE exome AF: 0.857

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.708 AC: 107569 AN: 151986 Hom.: 38858 Cov.: 31 AF XY: 0.700 AC XY: 52010 AN XY: 74274

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.784

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.695

Alfa AF: 0.749 Hom.: 14204

Bravo AF: 0.694

Asia WGS AF: 0.517 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.17
DANN	Benign	0.31

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: rs11637630; hg19: chr15-78899719;