15-78569175-C-T

Variant names:

• chr15-78569175-C-T
• rs7166003
• NM_000745.4:c.106+3350C>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.106+3350C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0356 in 152,250 control chromosomes in the GnomAD database, including 327 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 0.036 (327 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 3 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.119 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.106+3350C>T		intron	N/A	NP_000736.2
	CHRNA5	NM_001395171.1		c.106+3350C>T		intron	N/A	NP_001382100.1
	CHRNA5	NM_001395172.1		c.106+3350C>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.106+3350C>T		intron	N/A	ENSP00000299565.5
	CHRNA5	ENST00000913028.1		c.106+3350C>T		intron	N/A	ENSP00000583087.1
	CHRNA5	ENST00000559554.5	TSL:3	c.106+3350C>T		intron	N/A	ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.0356 AC: 5420 AN: 152132 Hom.: 328 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0129

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0253

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

GnomAD4 genome AF: 0.0356 AC: 5421 AN: 152250 Hom.: 327 Cov.: 32 AF XY: 0.0348 AC XY: 2594 AN XY: 74452

African (AFR) AF: 0.122 AC: 5072 AN: 41528

American (AMR) AF: 0.0129 AC: 197 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0199 AC: 69 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68026

Other (OTH) AF: 0.0251 AC: 53 AN: 2114

Alfa AF: 0.00807 Hom.: 27

Bravo AF: 0.0402

Asia WGS AF: 0.00607 AC: 22 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.80
DANN	Benign	0.19
PhyloP100		0.015
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: rs7166003; hg19: chr15-78861517;