rs1072003

Positions:

• chr8-42764858-C-G

Variant summary

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

The NM_004198.3(CHRNA6):​c.219+207G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 558,454 control chromosomes in the GnomAD database, including 20,028 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 0.31 (10248 hom., cov: 32)
  • Exomes 𝑓: 0.20 (9780 hom.)
• Consequence: CHRNA6 NM_004198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA6	NM_004198.3	c.219+207G>C		intron_variant		ENST00000276410.7	NP_004189.1
CHRNA6	NM_001199279.1	c.219+207G>C		intron_variant			NP_001186208.1
CHRNA6	XM_047422396.1	c.219+207G>C		intron_variant			XP_047278352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000276410.7	c.219+207G>C		intron_variant		1	NM_004198.3	ENSP00000276410	P1
CHRNA6	ENST00000533810.5	c.-19+207G>C		intron_variant		4		ENSP00000434659
CHRNA6	ENST00000534622.5	c.219+207G>C		intron_variant		2		ENSP00000433871
CHRNA6	ENST00000530869.1	n.421+207G>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47360 AN: 151912 Hom.: 10215 Cov.: 32

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.0956

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.308

GnomAD4 exome AF: 0.203 AC: 82562 AN: 406424 Hom.: 9780 AF XY: 0.202 AC XY: 42754 AN XY: 212142

Gnomad4 AFR exome AF: 0.614

Gnomad4 AMR exome AF: 0.290

Gnomad4 ASJ exome AF: 0.206

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.182

Gnomad4 OTH exome AF: 0.230

GnomAD4 genome AF: 0.312 AC: 47452 AN: 152030 Hom.: 10248 Cov.: 32 AF XY: 0.306 AC XY: 22773 AN XY: 74320

Gnomad4 AFR AF: 0.612

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.200

Gnomad4 FIN AF: 0.151

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.309

Alfa AF: 0.255 Hom.: 840

Bravo AF: 0.340

Asia WGS AF: 0.266 AC: 924 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.60

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: rs1072003; hg19: chr8-42620001;