rs16969949

Variant names:

• chr15-78574622-C-T
• rs16969949
• NM_000745.4:c.107-6189C>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.107-6189C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0394 in 152,066 control chromosomes in the GnomAD database, including 359 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 0.039 (359 hom., cov: 30)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.441
• Publications: 2 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.107-6189C>T		intron_variant	Intron 1 of 5	ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.107-6189C>T		intron_variant	Intron 1 of 5	1	NM_000745.4	ENSP00000299565.5
CHRNA5	ENST00000559554.5	c.107-6189C>T		intron_variant	Intron 1 of 5	3		ENSP00000453519.1

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 5999 AN: 151948 Hom.: 361 Cov.: 30

Gnomad AFR AF: 0.124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.0234

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00178

Gnomad OTH AF: 0.0321

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

GnomAD4 genome AF: 0.0394 AC: 5999 AN: 152066 Hom.: 359 Cov.: 30 AF XY: 0.0391 AC XY: 2908 AN XY: 74330

African (AFR) AF: 0.124 AC: 5134 AN: 41456

American (AMR) AF: 0.0147 AC: 224 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0234 AC: 81 AN: 3466

East Asian (EAS) AF: 0.0671 AC: 347 AN: 5170

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10564

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00178 AC: 121 AN: 68018

Other (OTH) AF: 0.0318 AC: 67 AN: 2110

Alfa AF: 0.0226 Hom.: 83

Bravo AF: 0.0443

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.66
DANN	Benign	0.42
PhyloP100		-0.44
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: rs16969949; hg19: chr15-78866964; COSMIC: COSV55141037;