rs7180002

Variant names:

• chr15-78581651-A-T
• rs7180002
• NM_000745.4:c.258+689A>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.258+689A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,138 control chromosomes in the GnomAD database, including 5,999 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 0.25 (5999 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.824
• Publications: 29 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 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.258+689A>T		intron	N/A	NP_000736.2
	CHRNA5	NM_001395171.1		c.258+689A>T		intron	N/A	NP_001382100.1
	CHRNA5	NM_001395172.1		c.258+689A>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.258+689A>T		intron	N/A	ENSP00000299565.5	P30532
	CHRNA5	ENST00000913028.1		c.258+689A>T		intron	N/A	ENSP00000583087.1
	CHRNA5	ENST00000394802.4	TSL:3	c.72+689A>T		intron	N/A	ENSP00000378281.4	H7BYM0

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38745 AN: 152020 Hom.: 5999 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.0329

Gnomad SAS AF: 0.222

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.255 AC: 38760 AN: 152138 Hom.: 5999 Cov.: 32 AF XY: 0.252 AC XY: 18728 AN XY: 74374

African (AFR) AF: 0.109 AC: 4537 AN: 41540

American (AMR) AF: 0.233 AC: 3553 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1316 AN: 3472

East Asian (EAS) AF: 0.0331 AC: 172 AN: 5192

South Asian (SAS) AF: 0.224 AC: 1081 AN: 4828

European-Finnish (FIN) AF: 0.328 AC: 3463 AN: 10556

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23542 AN: 67958

Other (OTH) AF: 0.287 AC: 605 AN: 2110

Alfa AF: 0.289 Hom.: 867

Bravo AF: 0.240

Asia WGS AF: 0.121 AC: 420 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.25
DANN	Benign	0.64
PhyloP100		-0.82
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: rs7180002; hg19: chr15-78873993;