rs12903575

Positions:

• chr15-78588745-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000745.4(CHRNA5):​c.413+322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 152,194 control chromosomes in the GnomAD database, including 111 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 0.032 (111 hom., cov: 32)
• Consequence: CHRNA5 NM_000745.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0318 (4844/152194) while in subpopulation NFE AF= 0.0504 (3426/68024). AF 95% confidence interval is 0.049. There are 111 homozygotes in gnomad4. There are 2261 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 111 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA5	NM_000745.4	c.413+322G>A		intron_variant		ENST00000299565.9	NP_000736.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA5	ENST00000299565.9	c.413+322G>A		intron_variant		1	NM_000745.4	ENSP00000299565	P1
CHRNA5	ENST00000394802.4	c.228+322G>A		intron_variant		3		ENSP00000378281
CHRNA5	ENST00000559554.5	c.413+322G>A		intron_variant		3		ENSP00000453519

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4844 AN: 152076 Hom.: 111 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0241

Gnomad ASJ AF: 0.0179

Gnomad EAS AF: 0.00866

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0503

Gnomad OTH AF: 0.0307

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

GnomAD4 genome AF: 0.0318 AC: 4844 AN: 152194 Hom.: 111 Cov.: 32 AF XY: 0.0304 AC XY: 2261 AN XY: 74398

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0240

Gnomad4 ASJ AF: 0.0179

Gnomad4 EAS AF: 0.00868

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.0263

Gnomad4 NFE AF: 0.0504

Gnomad4 OTH AF: 0.0299

Alfa AF: 0.0375 Hom.: 19

Bravo AF: 0.0309

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.1
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs12903575; hg19: chr15-78881087;