8-42774752-C-T

Variant names:

• chr8-42774752-C-T
• rs10107450
• ENST00000533810.5:c.-158-9548G>A

Variant summary

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

The ENST00000533810.5(CHRNA6):​c.-158-9548G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,110 control chromosomes in the GnomAD database, including 15,823 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 0.39 (15823 hom., cov: 32)
• Consequence: CHRNA6 ENST00000533810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 9 publications found

Genes affected

CHRNA6 (HGNC:15963): (cholinergic receptor nicotinic alpha 6 subunit) This gene encodes an alpha subunit of neuronal nicotinic acetylcholine receptors. These receptors consist of five subunits and function as ion channels involved in neurotransmission. The encoded protein is a subunit of neuronal nicotinic acetylcholine receptors that mediate dopaminergic neurotransmission and are activated by acetylcholine and exogenous nicotine. Alternatively spliced transcript variants have been observed for this gene. Single nucleotide polymorphisms in this gene have been associated with both nicotine and alcohol dependence. [provided by RefSeq, Dec 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 (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000533810.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA6	ENST00000533810.5	TSL:4	c.-158-9548G>A		intron	N/A	ENSP00000434659.1	E9PP97

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58570 AN: 151992 Hom.: 15777 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.364

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

GnomAD4 genome AF: 0.386 AC: 58673 AN: 152110 Hom.: 15823 Cov.: 32 AF XY: 0.380 AC XY: 28252 AN XY: 74364

African (AFR) AF: 0.767 AC: 31833 AN: 41490

American (AMR) AF: 0.336 AC: 5131 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 937 AN: 3470

East Asian (EAS) AF: 0.199 AC: 1026 AN: 5158

South Asian (SAS) AF: 0.296 AC: 1425 AN: 4822

European-Finnish (FIN) AF: 0.193 AC: 2048 AN: 10586

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15295 AN: 67992

Other (OTH) AF: 0.364 AC: 769 AN: 2114

Alfa AF: 0.271 Hom.: 27053

Bravo AF: 0.414

Asia WGS AF: 0.307 AC: 1069 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	0.12
DANN	Benign	0.61
PhyloP100		-1.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10107450; hg19: chr8-42629895;