rs2240320

Variant names:

• chr12-120158915-A-G
• rs2240320
• NM_006836.2:c.2750-300T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-120158915-A-G
• chr12-120158915-A-T

Variant summary

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

The NM_006836.2(GCN1):​c.2750-300T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,404 control chromosomes in the GnomAD database, including 6,321 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 0.25 (6321 hom., cov: 30)
• Consequence: GCN1 NM_006836.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 1 publications found

Genes affected

GCN1 (HGNC:4199): (GCN1 activator of EIF2AK4) Enables RNA binding activity and cadherin binding activity. Predicted to be involved in cellular response to leucine starvation and positive regulation of transcription from RNA polymerase II promoter in response to stress. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006836.2. 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
	GCN1	NM_006836.2	MANE Select	c.2750-300T>C		intron	N/A	NP_006827.1	Q92616

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GCN1	ENST00000300648.7	TSL:1 MANE Select	c.2750-300T>C		intron	N/A	ENSP00000300648.6	Q92616
	GCN1	ENST00000915860.1		c.2750-300T>C		intron	N/A	ENSP00000585919.1
	GCN1	ENST00000891846.1		c.2768-300T>C		intron	N/A	ENSP00000561905.1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 37945 AN: 151286 Hom.: 6291 Cov.: 30

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.248

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

GnomAD4 genome AF: 0.251 AC: 38014 AN: 151404 Hom.: 6321 Cov.: 30 AF XY: 0.252 AC XY: 18624 AN XY: 73970

African (AFR) AF: 0.441 AC: 18157 AN: 41180

American (AMR) AF: 0.170 AC: 2583 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3466

East Asian (EAS) AF: 0.558 AC: 2850 AN: 5104

South Asian (SAS) AF: 0.227 AC: 1088 AN: 4784

European-Finnish (FIN) AF: 0.142 AC: 1497 AN: 10514

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10059 AN: 67842

Other (OTH) AF: 0.245 AC: 513 AN: 2094

Alfa AF: 0.201 Hom.: 500

Bravo AF: 0.267

Asia WGS AF: 0.353 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	1.3
DANN	Benign	0.16
PhyloP100		-1.9
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2240320;

hg19: chr12-120596719;