Variant 12-6772917-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002286.6(LAG3):c.58+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,613,656 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 21 hom. )

Consequence

LAG3
NM_002286.6 splice_region, intron

Scores

Splicing: ADA: 0.0002742

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.60

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:

LAG3 (HGNC:):

LAG3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 12-6772917-C-T is Benign according to our data. Variant chr12-6772917-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 789317.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
LAG3	NM_002286.6 linkuse as main transcript	c.58+7C>T	splice_region_variant, intron_variant	ENST00000203629.3	NP_002277.4	P18627-1
LAG3	NM_001414176.1 linkuse as main transcript	c.58+7C>T	splice_region_variant, intron_variant		NP_001401105.1
LAG3	NM_001414177.1 linkuse as main transcript	c.58+7C>T	splice_region_variant, intron_variant		NP_001401106.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
LAG3	ENST00000203629.3 linkuse as main transcript	c.58+7C>T	splice_region_variant, intron_variant		1	NM_002286.6	ENSP00000203629.2	P18627-1
LAG3	ENST00000441671.6 linkuse as main transcript	c.58+7C>T	splice_region_variant, intron_variant		1		ENSP00000413825.2	P18627-2
LAG3	ENST00000538079.1 linkuse as main transcript	n.406C>T	non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

599

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.00420

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00530

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00606

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00365

AC:

917

AN:

250956

Hom.:

AF XY:

0.00346

AC XY:

470

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00249

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00101

Gnomad FIN exome

AF:

0.00516

Gnomad NFE exome

AF:

0.00565

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00510

AC:

7451

AN:

1461548

Hom.:

Cov.:

AF XY:

0.00492

AC XY:

3577

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.00233

Gnomad4 ASJ exome

AF:

0.000803

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000974

Gnomad4 FIN exome

AF:

0.00485

Gnomad4 NFE exome

AF:

0.00601

Gnomad4 OTH exome

AF:

0.00444

GnomAD4 genome

AF:

0.00394

AC:

599

AN:

152108

Hom.:

Cov.:

AF XY:

0.00361

AC XY:

268

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.000843

Gnomad4 AMR

AF:

0.00419

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00530

Gnomad4 NFE

AF:

0.00606

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00502

Hom.:

Bravo

AF:

0.00429

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00583

EpiControl

AF:

0.00492

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 21, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	LAG3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.20

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00027

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over