chr8-42759235-C-A

Position:

• chr8-42759235-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004198.3(CHRNA6):​c.220-122G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 732,570 control chromosomes in the GnomAD database, including 30,168 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 0.35 (13355 hom., cov: 31)
  • Exomes 𝑓: 0.22 (16813 hom.)
• Consequence: CHRNA6 NM_004198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17

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

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 = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA6	NM_004198.3	c.220-122G>T		intron_variant		ENST00000276410.7
CHRNA6	NM_001199279.1	c.220-2198G>T		intron_variant
CHRNA6	XM_047422396.1	c.220-122G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA6	ENST00000276410.7	c.220-122G>T		intron_variant		1	NM_004198.3	P1
CHRNA6	ENST00000533810.5	c.-18-122G>T		intron_variant		4
CHRNA6	ENST00000534622.5	c.220-2198G>T		intron_variant		2
CHRNA6	ENST00000530869.1	n.466-122G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53257 AN: 151908 Hom.: 13314 Cov.: 31

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.222 AC: 128944 AN: 580544 Hom.: 16813 Cov.: 7 AF XY: 0.218 AC XY: 68043 AN XY: 311684

Gnomad4 AFR exome AF: 0.713

Gnomad4 AMR exome AF: 0.310

Gnomad4 ASJ exome AF: 0.209

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.190

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.351 AC: 53356 AN: 152026 Hom.: 13355 Cov.: 31 AF XY: 0.345 AC XY: 25627 AN XY: 74304

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.214

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.333

Alfa AF: 0.239 Hom.: 3264

Bravo AF: 0.380

Asia WGS AF: 0.267 AC: 930 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	0.42
DANN	Benign	0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs892413; hg19: chr8-42614378;