15-78580777-C-T

Variant names:

• chr15-78580777-C-T
• rs569207
• NM_000745.4:c.107-34C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000745.4(CHRNA5):​c.107-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 1,551,828 control chromosomes in the GnomAD database, including 61,055 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 0.29 (7090 hom., cov: 32)
  • Exomes 𝑓: 0.26 (53965 hom.)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 51 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.107-34C>T		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.107-34C>T		intron_variant	Intron 1 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000559554.5	c.107-34C>T		intron_variant	Intron 1 of 5	3		ENSP00000453519.1
CHRNA5	ENST00000394802.4	c.-114C>T		upstream_gene_variant		3		ENSP00000378281.4

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43734 AN: 151726 Hom.: 7064 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.477

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.297

GnomAD2 exomes AF: 0.339 AC: 80363 AN: 236732 AF XY: 0.332

Gnomad AFR exome AF: 0.290

Gnomad AMR exome AF: 0.645

Gnomad ASJ exome AF: 0.236

Gnomad EAS exome AF: 0.469

Gnomad FIN exome AF: 0.305

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.314

GnomAD4 exome AF: 0.259 AC: 362273 AN: 1399984 Hom.: 53965 Cov.: 24 AF XY: 0.263 AC XY: 183234 AN XY: 696902

African (AFR) AF: 0.284 AC: 8968 AN: 31622

American (AMR) AF: 0.623 AC: 26037 AN: 41808

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 5439 AN: 24766

East Asian (EAS) AF: 0.502 AC: 19633 AN: 39094

South Asian (SAS) AF: 0.422 AC: 34552 AN: 81918

European-Finnish (FIN) AF: 0.295 AC: 15513 AN: 52570

Middle Eastern (MID) AF: 0.313 AC: 1402 AN: 4482

European-Non Finnish (NFE) AF: 0.220 AC: 234983 AN: 1065948

Other (OTH) AF: 0.273 AC: 15746 AN: 57776

GnomAD4 genome AF: 0.288 AC: 43793 AN: 151844 Hom.: 7090 Cov.: 32 AF XY: 0.296 AC XY: 21950 AN XY: 74188

African (AFR) AF: 0.285 AC: 11802 AN: 41374

American (AMR) AF: 0.478 AC: 7296 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 745 AN: 3468

East Asian (EAS) AF: 0.478 AC: 2475 AN: 5174

South Asian (SAS) AF: 0.429 AC: 2065 AN: 4818

European-Finnish (FIN) AF: 0.298 AC: 3126 AN: 10476

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15400 AN: 67968

Other (OTH) AF: 0.305 AC: 642 AN: 2108

Alfa AF: 0.264 Hom.: 10521

Bravo AF: 0.302

Asia WGS AF: 0.475 AC: 1651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.59
PhyloP100		-1.9
PromoterAI		0.011	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs569207; hg19: chr15-78873119; COSMIC: COSV55137493; COSMIC: COSV55137493;