rs2365094

Positions:

• chr12-6774504-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.512-91G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,418,704 control chromosomes in the GnomAD database, including 64,224 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 0.28 (6085 hom., cov: 33)
  • Exomes 𝑓: 0.30 (58139 hom.)
• Consequence: LAG3 NM_002286.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.428 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAG3	NM_002286.6	c.512-91G>C		intron_variant		ENST00000203629.3	NP_002277.4
LAG3	NM_001414176.1	c.512-91G>C		intron_variant			NP_001401105.1
LAG3	NM_001414177.1	c.512-91G>C		intron_variant			NP_001401106.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAG3	ENST00000203629.3	c.512-91G>C		intron_variant		1	NM_002286.6	ENSP00000203629	P2
LAG3	ENST00000441671.6	c.512-91G>C		intron_variant		1		ENSP00000413825	A2
LAG3	ENST00000538079.1	n.1134-91G>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42473 AN: 152018 Hom.: 6078 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.266

GnomAD4 exome AF: 0.299 AC: 379331 AN: 1266568 Hom.: 58139 AF XY: 0.299 AC XY: 187542 AN XY: 627678

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.348

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.322

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.294

Gnomad4 OTH exome AF: 0.297

GnomAD4 genome AF: 0.279 AC: 42508 AN: 152136 Hom.: 6085 Cov.: 33 AF XY: 0.283 AC XY: 21031 AN XY: 74378

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.319

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.443

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.266

Alfa AF: 0.289 Hom.: 823

Bravo AF: 0.271

Asia WGS AF: 0.385 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs2365094; hg19: chr12-6883670;