rs1882545

Positions:

• chr12-6776244-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000203629.3(LAG3):​c.1057+696G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 151,872 control chromosomes in the GnomAD database, including 23,461 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 0.54 (23461 hom., cov: 31)
• Consequence: LAG3 ENST00000203629.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAG3	NM_002286.6	c.1057+696G>A		intron_variant		ENST00000203629.3	NP_002277.4
LAG3	NM_001414176.1	c.1057+696G>A		intron_variant			NP_001401105.1
LAG3	NM_001414177.1	c.1057+696G>A		intron_variant			NP_001401106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAG3	ENST00000203629.3	c.1057+696G>A		intron_variant		1	NM_002286.6	ENSP00000203629	P2
LAG3	ENST00000538079.1	n.1679+696G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81719 AN: 151754 Hom.: 23454 Cov.: 31

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.538 AC: 81752 AN: 151872 Hom.: 23461 Cov.: 31 AF XY: 0.532 AC XY: 39478 AN XY: 74222

Gnomad4 AFR AF: 0.366

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.464

Gnomad4 FIN AF: 0.616

Gnomad4 NFE AF: 0.655

Gnomad4 OTH AF: 0.539

Alfa AF: 0.622 Hom.: 41120

Bravo AF: 0.527

Asia WGS AF: 0.361 AC: 1259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.52

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: rs1882545; hg19: chr12-6885410;