Variant rs2076355 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000228.3(LAMB3):c.298+50T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,231,534 control chromosomes in the GnomAD database, including 61,159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7612 hom., cov: 33)

Exomes 𝑓: 0.29 ( 53547 hom. )

Consequence

LAMB3
NM_000228.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.829

Variant links:

Genes affected

LAMB3 (HGNC:6490): (laminin subunit beta 3) The product encoded by this gene is a laminin that belongs to a family of basement membrane proteins. This protein is a beta subunit laminin, which together with an alpha and a gamma subunit, forms laminin-5. Mutations in this gene cause epidermolysis bullosa junctional Herlitz type, and generalized atrophic benign epidermolysis bullosa, diseases that are characterized by blistering of the skin. Multiple alternatively spliced transcript variants that encode the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

LAMB3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-209638484-A-T is Benign according to our data. Variant chr1-209638484-A-T is described in ClinVar as [Benign]. Clinvar id is 255593.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMB3	NM_000228.3 linkuse as main transcript	c.298+50T>A		intron_variant		ENST00000356082.9

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
LAMB3	ENST00000356082.9 linkuse as main transcript	c.298+50T>A	intron_variant	1	NM_000228.3	P1
LAMB3	ENST00000367030.7 linkuse as main transcript	c.298+50T>A	intron_variant	1		P1
LAMB3	ENST00000391911.5 linkuse as main transcript	c.298+50T>A	intron_variant	1		P1
LAMB3	ENST00000415782.1 linkuse as main transcript	c.298+50T>A	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.301

AC:

45228

AN:

150420

Hom.:

7599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.175

Gnomad AMR

AF:

0.404

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.722

Gnomad SAS

AF:

0.490

Gnomad FIN

AF:

0.237

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.307

GnomAD3 exomes

AF:

0.346

AC:

86095

AN:

249054

Hom.:

17777

AF XY:

0.344

AC XY:

46262

AN XY:

134676

show subpopulations

Gnomad AFR exome

AF:

0.323

Gnomad AMR exome

AF:

0.504

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.714

Gnomad SAS exome

AF:

0.473

Gnomad FIN exome

AF:

0.249

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.315

GnomAD4 exome

AF:

0.294

AC:

317628

AN:

1080994

Hom.:

53547

Cov.:

AF XY:

0.298

AC XY:

165111

AN XY:

554946

show subpopulations

Gnomad4 AFR exome

AF:

0.317

Gnomad4 AMR exome

AF:

0.496

Gnomad4 ASJ exome

AF:

0.232

Gnomad4 EAS exome

AF:

0.710

Gnomad4 SAS exome

AF:

0.472

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.247

Gnomad4 OTH exome

AF:

0.308

GnomAD4 genome

AF:

0.301

AC:

45278

AN:

150540

Hom.:

7612

Cov.:

AF XY:

0.310

AC XY:

22807

AN XY:

73602

show subpopulations

Gnomad4 AFR

AF:

0.322

Gnomad4 AMR

AF:

0.405

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.722

Gnomad4 SAS

AF:

0.489

Gnomad4 FIN

AF:

0.237

Gnomad4 NFE

AF:

0.235

Gnomad4 OTH

AF:

0.311

Alfa

AF:

0.256

Hom.:

1051

Bravo

AF:

0.313

Asia WGS

AF:

0.575

AC:

1998

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Amelogenesis imperfecta type 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

Junctional epidermolysis bullosa gravis of Herlitz

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 08, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.8

DANN

Benign

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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