rs892413

Variant names:

• chr8-42759235-C-A
• rs892413
• NM_004198.3:c.220-122G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-42759235-C-A
• chr8-42759235-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004198.3(CHRNA6):​c.220-122G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 732,570 control chromosomes in the GnomAD database, including 30,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.35 (13355 hom., cov: 31)
  • Exomes 𝑓: 0.22 (16813 hom.)
• Consequence: CHRNA6 NM_004198.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17
• Publications: 26 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004198.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA6	NM_004198.3	MANE Select	c.220-122G>T		intron	N/A	NP_004189.1	Q15825-1
	CHRNA6	NM_001199279.1		c.220-2198G>T		intron	N/A	NP_001186208.1	Q15825-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNA6	ENST00000276410.7	TSL:1 MANE Select	c.220-122G>T		intron	N/A	ENSP00000276410.3	Q15825-1
	CHRNA6	ENST00000534622.5	TSL:2	c.220-2198G>T		intron	N/A	ENSP00000433871.1	Q15825-2
	CHRNA6	ENST00000533810.5	TSL:4	c.-18-122G>T		intron	N/A	ENSP00000434659.1	E9PP97

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53257 AN: 151908 Hom.: 13314 Cov.: 31

Gnomad AFR AF: 0.710

Gnomad AMI AF: 0.102

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.222 AC: 128944 AN: 580544 Hom.: 16813 Cov.: 7 AF XY: 0.218 AC XY: 68043 AN XY: 311684

African (AFR) AF: 0.713 AC: 11167 AN: 15666

American (AMR) AF: 0.310 AC: 10414 AN: 33544

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 3652 AN: 17464

East Asian (EAS) AF: 0.184 AC: 6264 AN: 34094

South Asian (SAS) AF: 0.204 AC: 12120 AN: 59360

European-Finnish (FIN) AF: 0.190 AC: 8739 AN: 45902

Middle Eastern (MID) AF: 0.257 AC: 998 AN: 3890

European-Non Finnish (NFE) AF: 0.200 AC: 68091 AN: 340160

Other (OTH) AF: 0.246 AC: 7499 AN: 30464

GnomAD4 genome AF: 0.351 AC: 53356 AN: 152026 Hom.: 13355 Cov.: 31 AF XY: 0.345 AC XY: 25627 AN XY: 74304

African (AFR) AF: 0.710 AC: 29438 AN: 41458

American (AMR) AF: 0.308 AC: 4701 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3468

East Asian (EAS) AF: 0.214 AC: 1102 AN: 5158

South Asian (SAS) AF: 0.198 AC: 950 AN: 4804

European-Finnish (FIN) AF: 0.182 AC: 1923 AN: 10576

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13641 AN: 67994

Other (OTH) AF: 0.333 AC: 704 AN: 2114

Alfa AF: 0.241 Hom.: 3672

Bravo AF: 0.380

Asia WGS AF: 0.267 AC: 930 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.42
DANN	Benign	0.55
PhyloP100		-3.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs892413; hg19: chr8-42614378;