15-78588235-G-T

Variant names:

• chr15-78588235-G-T
• rs12898919
• NM_000745.4:c.304-79G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000745.4(CHRNA5):​c.304-79G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 537,042 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 13 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.304-79G>T		intron_variant	Intron 3 of 5	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.304-79G>T		intron_variant	Intron 3 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000394802.4	c.118-79G>T		intron_variant	Intron 2 of 4	3		ENSP00000378281.4
CHRNA5	ENST00000559554.5	c.304-79G>T		intron_variant	Intron 3 of 5	3		ENSP00000453519.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000186 AC: 1 AN: 537042 Hom.: 0 AF XY: 0.00000354 AC XY: 1 AN XY: 282774

African (AFR) AF: 0.00 AC: 0 AN: 13270

American (AMR) AF: 0.00 AC: 0 AN: 21724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14252

East Asian (EAS) AF: 0.00 AC: 0 AN: 31182

South Asian (SAS) AF: 0.00 AC: 0 AN: 40112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42738

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3628

European-Non Finnish (NFE) AF: 0.00000292 AC: 1 AN: 342604

Other (OTH) AF: 0.00 AC: 0 AN: 27532

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 8

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.58
DANN	Benign	0.53
PhyloP100		-1.0

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

Other links and lift over

dbSNP: rs12898919; hg19: chr15-78880577;