15-78578946-T-C

Variant names:

• chr15-78578946-T-C
• rs680244
• NM_000745.4:c.107-1865T>C

Variant summary

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

The NM_000745.4(CHRNA5):​c.107-1865T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,022 control chromosomes in the GnomAD database, including 28,141 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 0.61 (28141 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40
• Publications: 81 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	NM_000745.4	MANE Select	c.107-1865T>C		intron	N/A	NP_000736.2
	CHRNA5	NM_001395171.1		c.107-1865T>C		intron	N/A	NP_001382100.1
	CHRNA5	NM_001395172.1		c.107-1865T>C		intron	N/A	NP_001382101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA5	ENST00000299565.9	TSL:1 MANE Select	c.107-1865T>C		intron	N/A	ENSP00000299565.5
	CHRNA5	ENST00000559554.5	TSL:3	c.107-1865T>C		intron	N/A	ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91864 AN: 151902 Hom.: 28094 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.566

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.605 AC: 91979 AN: 152022 Hom.: 28141 Cov.: 32 AF XY: 0.610 AC XY: 45303 AN XY: 74302

African (AFR) AF: 0.576 AC: 23884 AN: 41444

American (AMR) AF: 0.730 AC: 11154 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.602 AC: 2088 AN: 3468

East Asian (EAS) AF: 0.753 AC: 3910 AN: 5190

South Asian (SAS) AF: 0.667 AC: 3217 AN: 4826

European-Finnish (FIN) AF: 0.624 AC: 6575 AN: 10534

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39058 AN: 67966

Other (OTH) AF: 0.641 AC: 1355 AN: 2114

Alfa AF: 0.589 Hom.: 116711

Bravo AF: 0.612

Asia WGS AF: 0.701 AC: 2439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.14
DANN	Benign	0.58
PhyloP100		-2.4
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: rs680244; hg19: chr15-78871288;