rs4887067

Positions:

• chr15-78594605-G-A

Variant summary

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

The NM_000745.4(CHRNA5):​c.*1352G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,310 control chromosomes in the GnomAD database, including 5,800 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 0.24 (5793 hom., cov: 32)
  • Exomes 𝑓: 0.23 (7 hom.)
• Consequence: CHRNA5 NM_000745.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.45

Genes affected

CHRNA5 (HGNC:1959): (cholinergic receptor nicotinic alpha 5 subunit) The protein encoded by this gene is a nicotinic acetylcholine receptor subunit and a member of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. These receptors are thought to be heteropentamers composed of separate but similar subunits. Defects in this gene have been linked to susceptibility to lung cancer type 2 (LNCR2).[provided by RefSeq, Jun 2010]

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.*1352G>A		3_prime_UTR_variant	6/6	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.*1352G>A		3_prime_UTR_variant	6/6	1	NM_000745.4	ENSP00000299565	P1
CHRNA3	ENST00000348639.7	c.1390-1414C>T		intron_variant		1		ENSP00000267951
CHRNA3	ENST00000559002.5	n.194-1414C>T		intron_variant, non_coding_transcript_variant		1
CHRNA3	ENST00000559658.5	c.*65-594C>T		intron_variant, NMD_transcript_variant		2		ENSP00000452896

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36641 AN: 152026 Hom.: 5792 Cov.: 32

Gnomad AFR AF: 0.0613

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.0324

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.235 AC: 39 AN: 166 Hom.: 7 Cov.: 0 AF XY: 0.225 AC XY: 27 AN XY: 120

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.241 AC: 36643 AN: 152144 Hom.: 5793 Cov.: 32 AF XY: 0.238 AC XY: 17722 AN XY: 74356

Gnomad4 AFR AF: 0.0612

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.222

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.274

Alfa AF: 0.281 Hom.: 859

Bravo AF: 0.225

Asia WGS AF: 0.115 AC: 403 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.82

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: rs4887067; hg19: chr15-78886947;