NM_000745.4:c.304-79G>C

Variant names:

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

Variant summary

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

The NM_000745.4(CHRNA5):​c.304-79G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0381 in 688,938 control chromosomes in the GnomAD database, including 615 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 0.031 (109 hom., cov: 32)
  • Exomes 𝑓: 0.040 (506 hom.)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0517 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0307 AC: 4674 AN: 152036 Hom.: 109 Cov.: 32

Gnomad AFR AF: 0.00930

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0153

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0504

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.0401 AC: 21544 AN: 536784 Hom.: 506 AF XY: 0.0392 AC XY: 11067 AN XY: 282632

Gnomad4 AFR exome AF: 0.00965

Gnomad4 AMR exome AF: 0.0188

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.0000641

Gnomad4 SAS exome AF: 0.0156

Gnomad4 FIN exome AF: 0.0285

Gnomad4 NFE exome AF: 0.0523

Gnomad4 OTH exome AF: 0.0331

GnomAD4 genome AF: 0.0307 AC: 4675 AN: 152154 Hom.: 109 Cov.: 32 AF XY: 0.0292 AC XY: 2173 AN XY: 74374

Gnomad4 AFR AF: 0.00930

Gnomad4 AMR AF: 0.0237

Gnomad4 ASJ AF: 0.0208

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0154

Gnomad4 FIN AF: 0.0264

Gnomad4 NFE AF: 0.0504

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0179 Hom.: 8

Bravo AF: 0.0297

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.59
DANN	Benign	0.59

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: rs12898919; hg19: chr15-78880577;