8-42759235-C-G

Variant names:

• chr8-42759235-C-G
• NM_004198.3:c.220-122G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004198.3(CHRNA6):​c.220-122G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000172 in 581,356 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000017 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNA6	NM_004198.3	c.220-122G>C		intron_variant	Intron 2 of 5	ENST00000276410.7	NP_004189.1
CHRNA6	NM_001199279.1	c.220-2198G>C		intron_variant	Intron 2 of 4		NP_001186208.1
CHRNA6	XM_047422396.1	c.220-122G>C		intron_variant	Intron 3 of 6		XP_047278352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNA6	ENST00000276410.7	c.220-122G>C		intron_variant	Intron 2 of 5	1	NM_004198.3	ENSP00000276410.3
CHRNA6	ENST00000534622.5	c.220-2198G>C		intron_variant	Intron 2 of 4	2		ENSP00000433871.1
CHRNA6	ENST00000533810.5	c.-18-122G>C		intron_variant	Intron 2 of 4	4		ENSP00000434659.1
CHRNA6	ENST00000530869.1	n.466-122G>C		intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000172 AC: 1 AN: 581356 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 312144

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000298

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.44
DANN	Benign	0.11

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-42614378;