12-6774504-G-A

Variant names:

• chr12-6774504-G-A
• rs2365094
• NM_002286.6:c.512-91G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002286.6(LAG3):​c.512-91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000788 in 1,268,882 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: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: LAG3 NM_002286.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 0 publications found

Genes affected

LAG3 (HGNC:6476): (lymphocyte activating 3) Lymphocyte-activation protein 3 belongs to Ig superfamily and contains 4 extracellular Ig-like domains. The LAG3 gene contains 8 exons. The sequence data, exon/intron organization, and chromosomal localization all indicate a close relationship of LAG3 to CD4. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002286.6. 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
	LAG3	NM_002286.6	MANE Select	c.512-91G>A		intron	N/A	NP_002277.4
	LAG3	NM_001414176.1		c.512-91G>A		intron	N/A	NP_001401105.1
	LAG3	NM_001414177.1		c.512-91G>A		intron	N/A	NP_001401106.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAG3	ENST00000203629.3	TSL:1 MANE Select	c.512-91G>A		intron	N/A	ENSP00000203629.2	P18627-1
	LAG3	ENST00000441671.6	TSL:1	c.512-91G>A		intron	N/A	ENSP00000413825.2	P18627-2
	LAG3	ENST00000887798.1		c.512-91G>A		intron	N/A	ENSP00000557857.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.88e-7 AC: 1 AN: 1268882 Hom.: 0 AF XY: 0.00000159 AC XY: 1 AN XY: 628788

African (AFR) AF: 0.00 AC: 0 AN: 28652

American (AMR) AF: 0.00 AC: 0 AN: 32016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20084

East Asian (EAS) AF: 0.00 AC: 0 AN: 38432

South Asian (SAS) AF: 0.00 AC: 0 AN: 70256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39798

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4870

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 981452

Other (OTH) AF: 0.0000188 AC: 1 AN: 53322

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.51
DANN	Benign	0.88
PhyloP100		-1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.27		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2365094; hg19: chr12-6883670;