rs55781567

Variant names:

• chr15-78565644-C-G
• rs55781567
• NM_000745.4:c.-76C>G

Variant summary

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

The NM_000745.4(CHRNA5):​c.-76C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 386,268 control chromosomes in the GnomAD database, including 20,054 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 0.30 (7373 hom., cov: 32)
  • Exomes 𝑓: 0.32 (12681 hom.)
• Consequence: CHRNA5 NM_000745.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 56 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.-76C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	ENST00000299565.9	NP_000736.2
CHRNA5	NM_000745.4	c.-76C>G		5_prime_UTR_variant	Exon 1 of 6	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.-76C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000299565.9	c.-76C>G		5_prime_UTR_variant	Exon 1 of 6	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000559554.5	c.-76C>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 6	3		ENSP00000453519.1
CHRNA5	ENST00000559554.5	c.-76C>G		5_prime_UTR_variant	Exon 1 of 6	3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45942 AN: 151668 Hom.: 7361 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.351

Gnomad OTH AF: 0.323

GnomAD4 exome AF: 0.320 AC: 74987 AN: 234490 Hom.: 12681 Cov.: 5 AF XY: 0.318 AC XY: 37269 AN XY: 117054

African (AFR) AF: 0.258 AC: 1271 AN: 4922

American (AMR) AF: 0.228 AC: 658 AN: 2880

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1237 AN: 3560

East Asian (EAS) AF: 0.0229 AC: 150 AN: 6538

South Asian (SAS) AF: 0.236 AC: 938 AN: 3976

European-Finnish (FIN) AF: 0.337 AC: 3136 AN: 9304

Middle Eastern (MID) AF: 0.370 AC: 719 AN: 1944

European-Non Finnish (NFE) AF: 0.334 AC: 63771 AN: 191006

Other (OTH) AF: 0.300 AC: 3107 AN: 10360

GnomAD4 genome AF: 0.303 AC: 45989 AN: 151778 Hom.: 7373 Cov.: 32 AF XY: 0.299 AC XY: 22153 AN XY: 74168

African (AFR) AF: 0.272 AC: 11276 AN: 41458

American (AMR) AF: 0.250 AC: 3811 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1241 AN: 3468

East Asian (EAS) AF: 0.0340 AC: 175 AN: 5150

South Asian (SAS) AF: 0.227 AC: 1092 AN: 4818

European-Finnish (FIN) AF: 0.327 AC: 3421 AN: 10452

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.351 AC: 23797 AN: 67858

Other (OTH) AF: 0.321 AC: 678 AN: 2112

Alfa AF: 0.320 Hom.: 996

Bravo AF: 0.295

Asia WGS AF: 0.136 AC: 477 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.8
DANN	Benign	0.49
PhyloP100		-1.0
PromoterAI		-0.029	Neutral
Mutation Taster		=287/13	polymorphism (auto)

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: rs55781567; hg19: chr15-78857986;