rs11633585

chr15-78582150-A-C

Variant summary

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

The NM_000745.4(CHRNA5):c.258+1188A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 152,216 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: -0.707

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=-1.02).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0321 (4886/152216) while in subpopulation NFE AF= 0.0508 (3457/68010). AF 95% confidence interval is 0.0494. There are 111 homozygotes in gnomad4. There are 2280 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 111 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA5	NM_000745.4	c.258+1188A>C		intron_variant		ENST00000299565.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA5	ENST00000299565.9	c.258+1188A>C		intron_variant		1	NM_000745.4	P1
CHRNA5	ENST00000394802.4	c.73+1188A>C		intron_variant		3
CHRNA5	ENST00000559554.5	c.258+1188A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.0321 AC: 4886 AN: 152098 Hom.: 111 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.00866

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0274

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.0302

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

GnomAD4 genome AF: 0.0321 AC: 4886 AN: 152216 Hom.: 111 Cov.: 32 AF XY: 0.0306 AC XY: 2280 AN XY: 74416

Gnomad4 AFR AF: 0.0117

Gnomad4 AMR AF: 0.0238

Gnomad4 ASJ AF: 0.0208

Gnomad4 EAS AF: 0.00868

Gnomad4 SAS AF: 0.0195

Gnomad4 FIN AF: 0.0274

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.0294

Alfa AF: 0.0380 Hom.: 17

Bravo AF: 0.0312

Asia WGS AF: 0.0170 AC: 59 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	1.2
Dann	Benign	0.61

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: rs11633585; hg19: chr15-78874492;