rs3782735

Positions:

• chr12-6775910-G-A
• chr12-6775910-G-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAG3	NM_002286.6	c.1057+362G>A		intron_variant		ENST00000203629.3	NP_002277.4
LAG3	NM_001414176.1	c.1057+362G>A		intron_variant			NP_001401105.1
LAG3	NM_001414177.1	c.1057+362G>A		intron_variant			NP_001401106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAG3	ENST00000203629.3	c.1057+362G>A		intron_variant		1	NM_002286.6	ENSP00000203629	P2
LAG3	ENST00000538079.1	n.1679+362G>A		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.625

Alfa AF: 0.595 Hom.: 34571

Bravo AF: 0.646

Asia WGS AF: 0.605 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.82

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: rs3782735; hg19: chr12-6885076;