12-6775910-G-A

Variant names:

• chr12-6775910-G-A
• rs3782735
• NM_002286.6:c.1057+362G>A

Variant summary

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

The NM_002286.6(LAG3):​c.1057+362G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.635 in 152,090 control chromosomes in the GnomAD database, including 31,070 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 0.63 (31070 hom., cov: 32)
• Consequence: LAG3 NM_002286.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.40
• Publications: 32 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAG3	NM_002286.6	MANE Select	c.1057+362G>A		intron	N/A	NP_002277.4
	LAG3	NM_001414176.1		c.1057+362G>A		intron	N/A	NP_001401105.1
	LAG3	NM_001414177.1		c.1057+362G>A		intron	N/A	NP_001401106.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAG3	ENST00000203629.3	TSL:1 MANE Select	c.1057+362G>A		intron	N/A	ENSP00000203629.2
	LAG3	ENST00000538079.1	TSL:2	n.1679+362G>A		intron	N/A
	LAG3	ENST00000441671.6	TSL:1	c.*336G>A		downstream_gene	N/A	ENSP00000413825.2

Frequencies

GnomAD3 genomes AF: 0.635 AC: 96430 AN: 151972 Hom.: 31035 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.635 AC: 96520 AN: 152090 Hom.: 31070 Cov.: 32 AF XY: 0.629 AC XY: 46758 AN XY: 74352

African (AFR) AF: 0.754 AC: 31314 AN: 41516

American (AMR) AF: 0.581 AC: 8866 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2162 AN: 3470

East Asian (EAS) AF: 0.604 AC: 3128 AN: 5176

South Asian (SAS) AF: 0.611 AC: 2945 AN: 4818

European-Finnish (FIN) AF: 0.542 AC: 5721 AN: 10556

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40317 AN: 67972

Other (OTH) AF: 0.625 AC: 1319 AN: 2110

Alfa AF: 0.607 Hom.: 83908

Bravo AF: 0.646

Asia WGS AF: 0.605 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.82
PhyloP100		1.4
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: rs3782735; hg19: chr12-6885076;