chr8-42795293-C-G

Position:

• chr8-42795293-C-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
		n.42795293C>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000533810.5	c.-159+1040G>C		intron_variant		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

Gnomad4 AFR AF: 0.639

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.214

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.329

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4737071; hg19: chr8-42650436;