rs6474417

Variant names:

• chr8-42774377-A-C
• rs6474417
• ENST00000533810.5:c.-158-9173T>G

Your query was ambiguous. Multiple possible variants found:

• chr8-42774377-A-C
• chr8-42774377-A-G

Variant summary

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

The ENST00000533810.5(CHRNA6):​c.-158-9173T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.948 in 152,240 control chromosomes in the GnomAD database, including 68,404 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 0.95 (68404 hom., cov: 31)
• Consequence: CHRNA6 ENST00000533810.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616
• Publications: 1 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=-1.09).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.-158-9173T>G		intron_variant	Intron 1 of 4	4		ENSP00000434659.1

Frequencies

GnomAD3 genomes AF: 0.947 AC: 144134 AN: 152122 Hom.: 68339 Cov.: 31

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.966

Gnomad AMR AF: 0.948

Gnomad ASJ AF: 0.929

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.964

Gnomad MID AF: 0.956

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.931

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

GnomAD4 genome AF: 0.948 AC: 144257 AN: 152240 Hom.: 68404 Cov.: 31 AF XY: 0.950 AC XY: 70680 AN XY: 74424

African (AFR) AF: 0.956 AC: 39682 AN: 41530

American (AMR) AF: 0.948 AC: 14488 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.929 AC: 3223 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5171 AN: 5172

South Asian (SAS) AF: 0.989 AC: 4767 AN: 4820

European-Finnish (FIN) AF: 0.964 AC: 10231 AN: 10618

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.934 AC: 63562 AN: 68022

Other (OTH) AF: 0.931 AC: 1971 AN: 2116

Alfa AF: 0.942 Hom.: 56952

Bravo AF: 0.945

Asia WGS AF: 0.990 AC: 3444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	2.0
DANN	Benign	0.49
PhyloP100		-0.62

Splicing

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

Other links and lift over

dbSNP: rs6474417; hg19: chr8-42629520;