chr8-42763570-C-A

Position:

• chr8-42763570-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.219+1495G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 152,190 control chromosomes in the GnomAD database, including 401 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 0.057 (401 hom., cov: 32)
• Consequence: CHRNA6 NM_004198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNA6	NM_004198.3	c.219+1495G>T		intron_variant		ENST00000276410.7	NP_004189.1
CHRNA6	NM_001199279.1	c.219+1495G>T		intron_variant			NP_001186208.1
CHRNA6	XM_047422396.1	c.219+1495G>T		intron_variant			XP_047278352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000276410.7	c.219+1495G>T		intron_variant		1	NM_004198.3	ENSP00000276410	P1
CHRNA6	ENST00000533810.5	c.-19+1495G>T		intron_variant		4		ENSP00000434659
CHRNA6	ENST00000534622.5	c.219+1495G>T		intron_variant		2		ENSP00000433871
CHRNA6	ENST00000530869.1	n.421+1495G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0567 AC: 8618 AN: 152072 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.0173

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.0816

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.0660

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

GnomAD4 genome AF: 0.0566 AC: 8617 AN: 152190 Hom.: 401 Cov.: 32 AF XY: 0.0625 AC XY: 4651 AN XY: 74382

Gnomad4 AFR AF: 0.0172

Gnomad4 AMR AF: 0.0463

Gnomad4 ASJ AF: 0.0816

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.0226

Gnomad4 FIN AF: 0.174

Gnomad4 NFE AF: 0.0543

Gnomad4 OTH AF: 0.0677

Alfa AF: 0.0529 Hom.: 355

Bravo AF: 0.0473

Asia WGS AF: 0.114 AC: 396 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.67
DANN	Benign	0.35

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: rs16891604; hg19: chr8-42618713;