chr8-42761725-T-C

Position:

• chr8-42761725-T-C

Variant summary

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

The NM_004198.3(CHRNA6):​c.220-2612A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,174 control chromosomes in the GnomAD database, including 13,991 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 0.36 (13991 hom., cov: 33)
• Consequence: CHRNA6 NM_004198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNA6	NM_004198.3	c.220-2612A>G		intron_variant		ENST00000276410.7
CHRNA6	NM_001199279.1	c.219+3340A>G		intron_variant
CHRNA6	XM_047422396.1	c.220-2612A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNA6	ENST00000276410.7	c.220-2612A>G		intron_variant		1	NM_004198.3	P1
CHRNA6	ENST00000533810.5	c.-18-2612A>G		intron_variant		4
CHRNA6	ENST00000534622.5	c.219+3340A>G		intron_variant		2
CHRNA6	ENST00000530869.1	n.422-2321A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54243 AN: 152056 Hom.: 13943 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.357 AC: 54351 AN: 152174 Hom.: 13991 Cov.: 33 AF XY: 0.351 AC XY: 26136 AN XY: 74412

Gnomad4 AFR AF: 0.730

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.335

Alfa AF: 0.301 Hom.: 2191

Bravo AF: 0.386

Asia WGS AF: 0.272 AC: 946 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
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: rs10087172; hg19: chr8-42616868;