8-42754708-C-T

Variant names:

• chr8-42754708-C-T
• rs35389610
• NM_004198.3:c.1353+1138G>A

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_004198.3(CHRNA6):​c.1353+1138G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00438 in 152,260 control chromosomes in the GnomAD database, including 4 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 0.0044 (4 hom., cov: 32)
• Consequence: CHRNA6 NM_004198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.663
• Publications: 3 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA6	NM_004198.3	c.1353+1138G>A		intron_variant	Intron 5 of 5	ENST00000276410.7	NP_004189.1
CHRNA6	NM_001199279.1	c.1308+1138G>A		intron_variant	Intron 4 of 4		NP_001186208.1
CHRNA6	XM_047422396.1	c.1353+1138G>A		intron_variant	Intron 6 of 6		XP_047278352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000276410.7	c.1353+1138G>A		intron_variant	Intron 5 of 5	1	NM_004198.3	ENSP00000276410.3
CHRNA6	ENST00000534622.5	c.1308+1138G>A		intron_variant	Intron 4 of 4	2		ENSP00000433871.1

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 667 AN: 152142 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00130

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00760

Gnomad OTH AF: 0.00335

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

GnomAD4 genome AF: 0.00438 AC: 667 AN: 152260 Hom.: 4 Cov.: 32 AF XY: 0.00378 AC XY: 281 AN XY: 74430

African (AFR) AF: 0.00130 AC: 54 AN: 41554

American (AMR) AF: 0.00393 AC: 60 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4824

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00760 AC: 517 AN: 68018

Other (OTH) AF: 0.00331 AC: 7 AN: 2114

Alfa AF: 0.00273 Hom.: 1

Bravo AF: 0.00457

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.62
DANN	Benign	0.73
PhyloP100		0.66
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs35389610; hg19: chr8-42609851;