12-6776244-G-C

Variant names:

• chr12-6776244-G-C
• rs1882545
• NM_002286.6:c.1057+696G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002286.6(LAG3):​c.1057+696G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: LAG3 NM_002286.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAG3	NM_002286.6	c.1057+696G>C		intron_variant	Intron 5 of 7	ENST00000203629.3	NP_002277.4
LAG3	NM_001414176.1	c.1057+696G>C		intron_variant	Intron 5 of 7		NP_001401105.1
LAG3	NM_001414177.1	c.1057+696G>C		intron_variant	Intron 5 of 6		NP_001401106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAG3	ENST00000203629.3	c.1057+696G>C		intron_variant	Intron 5 of 7	1	NM_002286.6	ENSP00000203629.2
LAG3	ENST00000538079.1	n.1679+696G>C		intron_variant	Intron 4 of 5	2

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		-0.016

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: rs1882545; hg19: chr12-6885410;