8-42795293-C-G

Variant names:

• chr8-42795293-C-G
• rs4737071
• ENST00000533810.5:c.-159+1040G>C

Variant summary

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

The ENST00000533810.5(CHRNA6):​c.-159+1040G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,976 control chromosomes in the GnomAD database, including 11,285 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 0.33 (11285 hom., cov: 33)
• Consequence: CHRNA6 ENST00000533810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• Publications: 2 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000533810.5	c.-159+1040G>C		intron_variant	Intron 1 of 4	4		ENSP00000434659.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50020 AN: 151858 Hom.: 11255 Cov.: 33

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.330 AC: 50105 AN: 151976 Hom.: 11285 Cov.: 33 AF XY: 0.324 AC XY: 24033 AN XY: 74260

African (AFR) AF: 0.639 AC: 26479 AN: 41446

American (AMR) AF: 0.308 AC: 4702 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 741 AN: 3470

East Asian (EAS) AF: 0.185 AC: 954 AN: 5160

South Asian (SAS) AF: 0.251 AC: 1205 AN: 4810

European-Finnish (FIN) AF: 0.140 AC: 1473 AN: 10542

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13668 AN: 67968

Other (OTH) AF: 0.329 AC: 693 AN: 2106

Alfa AF: 0.104 Hom.: 136

Bravo AF: 0.358

Asia WGS AF: 0.284 AC: 989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.33
PhyloP100		0.21

Splicing

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

Other links and lift over

dbSNP: rs4737071; hg19: chr8-42650436;