NM_000745.4:c.107-3223C>T

Variant names:

• chr15-78577588-C-T
• rs495956
• NM_000745.4:c.107-3223C>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.107-3223C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.638 in 151,912 control chromosomes in the GnomAD database, including 31,239 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 0.64 (31239 hom., cov: 31)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.106
• Publications: 11 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000745.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	NM_000745.4	MANE Select	c.107-3223C>T		intron	N/A	NP_000736.2
	CHRNA5	NM_001395171.1		c.107-3223C>T		intron	N/A	NP_001382100.1
	CHRNA5	NM_001395172.1		c.107-3223C>T		intron	N/A	NP_001382101.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	ENST00000299565.9	TSL:1 MANE Select	c.107-3223C>T		intron	N/A	ENSP00000299565.5	P30532
	CHRNA5	ENST00000913028.1		c.107-3223C>T		intron	N/A	ENSP00000583087.1
	CHRNA5	ENST00000559554.5	TSL:3	c.107-3223C>T		intron	N/A	ENSP00000453519.1	H0YM98

Frequencies

GnomAD3 genomes AF: 0.638 AC: 96873 AN: 151792 Hom.: 31194 Cov.: 31

Gnomad AFR AF: 0.590

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.685

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.668

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

GnomAD4 genome AF: 0.638 AC: 96981 AN: 151912 Hom.: 31239 Cov.: 31 AF XY: 0.642 AC XY: 47632 AN XY: 74240

African (AFR) AF: 0.590 AC: 24411 AN: 41372

American (AMR) AF: 0.755 AC: 11532 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.631 AC: 2189 AN: 3468

East Asian (EAS) AF: 0.762 AC: 3947 AN: 5178

South Asian (SAS) AF: 0.687 AC: 3305 AN: 4812

European-Finnish (FIN) AF: 0.653 AC: 6877 AN: 10530

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42548 AN: 67958

Other (OTH) AF: 0.672 AC: 1419 AN: 2112

Alfa AF: 0.618 Hom.: 3756

Bravo AF: 0.644

Asia WGS AF: 0.719 AC: 2501 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.7
DANN	Benign	0.37
PhyloP100		0.11
Mutation Taster		=100/0	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: rs495956; hg19: chr15-78869930;