Variant chr1-209632550-C-G 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.822+33G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 1,590,144 control chromosomes in the GnomAD database, including 15,229 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1330 hom., cov: 33)

Exomes 𝑓: 0.13 ( 13899 hom. )

Consequence

LAMB3
NM_000228.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.421

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 1-209632550-C-G is Benign according to our data. Variant chr1-209632550-C-G is described in ClinVar as [Benign]. Clinvar id is 255597.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMB3	NM_000228.3 linkuse as main transcript	c.822+33G>C		intron_variant		ENST00000356082.9	NP_000219.2	Q13751A0A0S2Z3R6

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
LAMB3	ENST00000356082.9 linkuse as main transcript	c.822+33G>C	intron_variant	1	NM_000228.3	ENSP00000348384.3	Q13751
LAMB3	ENST00000367030.7 linkuse as main transcript	c.822+33G>C	intron_variant	1		ENSP00000355997.3	Q13751
LAMB3	ENST00000391911.5 linkuse as main transcript	c.822+33G>C	intron_variant	1		ENSP00000375778.1	Q13751

Frequencies

GnomAD3 genomes

AF:

0.125

AC:

19029

AN:

152170

Hom.:

1331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0805

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.230

Gnomad EAS

AF:

0.0755

Gnomad SAS

AF:

0.0925

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.138

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.136

AC:

33487

AN:

246656

Hom.:

2548

AF XY:

0.133

AC XY:

17853

AN XY:

134204

show subpopulations

Gnomad AFR exome

AF:

0.0802

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.245

Gnomad EAS exome

AF:

0.0787

Gnomad SAS exome

AF:

0.0889

Gnomad FIN exome

AF:

0.176

Gnomad NFE exome

AF:

0.140

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.135

AC:

193419

AN:

1437856

Hom.:

13899

Cov.:

AF XY:

0.134

AC XY:

95612

AN XY:

716100

show subpopulations

Gnomad4 AFR exome

AF:

0.0752

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.0980

Gnomad4 SAS exome

AF:

0.0890

Gnomad4 FIN exome

AF:

0.177

Gnomad4 NFE exome

AF:

0.136

Gnomad4 OTH exome

AF:

0.129

GnomAD4 genome

AF:

0.125

AC:

19044

AN:

152288

Hom.:

1330

Cov.:

AF XY:

0.126

AC XY:

9412

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0805

Gnomad4 AMR

AF:

0.147

Gnomad4 ASJ

AF:

0.230

Gnomad4 EAS

AF:

0.0753

Gnomad4 SAS

AF:

0.0928

Gnomad4 FIN

AF:

0.187

Gnomad4 NFE

AF:

0.138

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.110

Hom.:

253

Bravo

AF:

0.120

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.79

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

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