rs2240320

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GCN1	NM_006836.2	c.2750-300T>C		intron_variant		ENST00000300648.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GCN1	ENST00000300648.7	c.2750-300T>C		intron_variant		1	NM_006836.2	P1
GCN1	ENST00000547369.5	n.362-300T>C		intron_variant, non_coding_transcript_variant		3
GCN1	ENST00000550471.1	n.763-300T>C		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.245

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 v4.3

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

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: rs2240320; hg19: chr12-120596719;