8-42780156-A-G

Variant names:

• chr8-42780156-A-G
• rs6474419
• ENST00000533810.5:c.-158-14952T>C

Variant summary

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

The ENST00000533810.5(CHRNA6):​c.-158-14952T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,174 control chromosomes in the GnomAD database, including 3,445 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 0.15 (3445 hom., cov: 32)
• Consequence: CHRNA6 ENST00000533810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 3 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.371 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.-158-14952T>C		intron	N/A	ENSP00000434659.1	E9PP97

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23409 AN: 152056 Hom.: 3439 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.0793

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.154 AC: 23454 AN: 152174 Hom.: 3445 Cov.: 32 AF XY: 0.155 AC XY: 11561 AN XY: 74414

African (AFR) AF: 0.376 AC: 15607 AN: 41466

American (AMR) AF: 0.172 AC: 2630 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0793 AC: 275 AN: 3470

East Asian (EAS) AF: 0.194 AC: 1007 AN: 5182

South Asian (SAS) AF: 0.139 AC: 673 AN: 4830

European-Finnish (FIN) AF: 0.0418 AC: 444 AN: 10614

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0355 AC: 2415 AN: 67998

Other (OTH) AF: 0.160 AC: 338 AN: 2114

Alfa AF: 0.0803 Hom.: 263

Bravo AF: 0.177

Asia WGS AF: 0.213 AC: 739 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.3
DANN	Benign	0.89
PhyloP100		0.12

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6474419; hg19: chr8-42635299;