Genetic Variant NM_002286.6:c.512-91G>A (chr12-6774504-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002286.6(LAG3):c.512-91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000788 in 1,268,882 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 33)

Exomes 𝑓: 7.9e-7 ( 0 hom. )

Consequence

LAG3
NM_002286.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.11

Publications

0 publications found

Variant links:

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]

LAG3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
LAG3	NM_002286.6 link	c.512-91G>A	intron_variant	Intron 3 of 7	ENST00000203629.3	NP_002277.4	P18627-1
LAG3	NM_001414176.1 link	c.512-91G>A	intron_variant	Intron 3 of 7		NP_001401105.1
LAG3	NM_001414177.1 link	c.512-91G>A	intron_variant	Intron 3 of 6		NP_001401106.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAG3	ENST00000203629.3 link	c.512-91G>A	intron_variant	Intron 3 of 7	1	NM_002286.6	ENSP00000203629.2	P18627-1
LAG3	ENST00000441671.6 link	c.512-91G>A	intron_variant	Intron 3 of 4	1		ENSP00000413825.2	P18627-2
LAG3	ENST00000538079.1 link	n.1134-91G>A	intron_variant	Intron 2 of 5	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.88e-7

AC:

AN:

1268882

Hom.:

AF XY:

0.00000159

AC XY:

AN XY:

628788

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28652

American (AMR)

AF:

0.00

AC:

AN:

32016

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20084

East Asian (EAS)

AF:

0.00

AC:

AN:

38432

South Asian (SAS)

AF:

0.00

AC:

AN:

70256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39798

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4870

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

981452

Other (OTH)

AF:

0.0000188

AC:

AN:

53322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.51

(source)

DANN

Benign

0.88

PhyloP100

-1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.27

Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over