chr15-78574700-C-G

Variant names:

• chr15-78574700-C-G
• rs12903839
• NM_000745.4:c.107-6111C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000745.4(CHRNA5):​c.107-6111C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 152,072 control chromosomes in the GnomAD database, including 112 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 0.033 (112 hom., cov: 30)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0325 (4944/152072) while in subpopulation NFE AF = 0.051 (3465/67984). AF 95% confidence interval is 0.0496. There are 112 homozygotes in GnomAd4. There are 2309 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 112 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.107-6111C>G		intron_variant	Intron 1 of 5	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.107-6111C>G		intron_variant	Intron 1 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000559554.5	c.107-6111C>G		intron_variant	Intron 1 of 5	3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4943 AN: 151954 Hom.: 112 Cov.: 30

Gnomad AFR AF: 0.0129

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.0244

Gnomad ASJ AF: 0.0205

Gnomad EAS AF: 0.00868

Gnomad SAS AF: 0.0193

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0509

Gnomad OTH AF: 0.0306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0325 AC: 4944 AN: 152072 Hom.: 112 Cov.: 30 AF XY: 0.0311 AC XY: 2309 AN XY: 74334

African (AFR) AF: 0.0129 AC: 534 AN: 41512

American (AMR) AF: 0.0243 AC: 371 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0205 AC: 71 AN: 3464

East Asian (EAS) AF: 0.00870 AC: 45 AN: 5172

South Asian (SAS) AF: 0.0194 AC: 93 AN: 4806

European-Finnish (FIN) AF: 0.0272 AC: 287 AN: 10564

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0510 AC: 3465 AN: 67984

Other (OTH) AF: 0.0298 AC: 63 AN: 2112

Alfa AF: 0.0382 Hom.: 17

Bravo AF: 0.0315

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.84
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism

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: rs12903839; hg19: chr15-78867042;