rs514743

Variant names:

• chr15-78591885-T-A
• rs514743
• NM_000745.4:c.1246-1207T>A

Your query was ambiguous. Multiple possible variants found:

• chr15-78591885-T-A
• chr15-78591885-T-C
• chr15-78591885-T-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.1246-1207T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,106 control chromosomes in the GnomAD database, including 36,753 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 0.69 (36753 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 40 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.1246-1207T>A		intron_variant	Intron 5 of 5	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.1246-1207T>A		intron_variant	Intron 5 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000394802.4	c.522-1207T>A		intron_variant	Intron 4 of 4	3		ENSP00000378281.4
CHRNA5	ENST00000559554.5	c.459-1207T>A		intron_variant	Intron 5 of 5	3		ENSP00000453519.1
CHRNA5	ENST00000559576.1	c.144-1207T>A		intron_variant	Intron 1 of 1	3		ENSP00000452641.1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105030 AN: 151988 Hom.: 36700 Cov.: 32

Gnomad AFR AF: 0.762

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.654

Gnomad EAS AF: 0.819

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.707

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

GnomAD4 genome AF: 0.691 AC: 105146 AN: 152106 Hom.: 36753 Cov.: 32 AF XY: 0.693 AC XY: 51568 AN XY: 74360

African (AFR) AF: 0.762 AC: 31599 AN: 41482

American (AMR) AF: 0.772 AC: 11804 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.654 AC: 2270 AN: 3470

East Asian (EAS) AF: 0.819 AC: 4246 AN: 5182

South Asian (SAS) AF: 0.691 AC: 3332 AN: 4824

European-Finnish (FIN) AF: 0.650 AC: 6859 AN: 10558

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42771 AN: 67992

Other (OTH) AF: 0.710 AC: 1496 AN: 2106

Alfa AF: 0.521 Hom.: 1344

Bravo AF: 0.705

Asia WGS AF: 0.753 AC: 2621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.33
DANN	Benign	0.34
PhyloP100		0.26
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: rs514743; hg19: chr15-78884227;