dbSNP rs2566: LAMB3:c.*102C>T (chr1-209615169-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000228.3(LAMB3):c.*102C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,486,242 control chromosomes in the GnomAD database, including 57,455 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5835 hom., cov: 33)

Exomes 𝑓: 0.28 ( 51620 hom. )

Consequence

LAMB3
NM_000228.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.14

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 1-209615169-G-A is Benign according to our data. Variant chr1-209615169-G-A is described in ClinVar as [Benign]. Clinvar id is 295059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMB3	NM_000228.3 link	c.*102C>T		3_prime_UTR_variant	Exon 23 of 23	ENST00000356082.9	NP_000219.2	Q13751A0A0S2Z3R6

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMB3	ENST00000356082 link	c.*102C>T	3_prime_UTR_variant	Exon 23 of 23	1	NM_000228.3	ENSP00000348384.3	Q13751
LAMB3	ENST00000367030 link	c.*102C>T	3_prime_UTR_variant	Exon 23 of 23	1		ENSP00000355997.3	Q13751
LAMB3	ENST00000391911 link	c.*102C>T	3_prime_UTR_variant	Exon 22 of 22	1		ENSP00000375778.1	Q13751

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41644

AN:

152008

Hom.:

5818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.248

Gnomad AMI

AF:

0.207

Gnomad AMR

AF:

0.351

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.346

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.274

Gnomad OTH

AF:

0.284

GnomAD4 exome

AF:

0.275

AC:

367048

AN:

1334116

Hom.:

51620

Cov.:

AF XY:

0.273

AC XY:

182649

AN XY:

668618

show subpopulations

Gnomad4 AFR exome

AF:

0.253

Gnomad4 AMR exome

AF:

0.412

Gnomad4 ASJ exome

AF:

0.188

Gnomad4 EAS exome

AF:

0.337

Gnomad4 SAS exome

AF:

0.267

Gnomad4 FIN exome

AF:

0.276

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.269

GnomAD4 genome

AF:

0.274

AC:

41703

AN:

152126

Hom.:

5835

Cov.:

AF XY:

0.274

AC XY:

20411

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.248

Gnomad4 AMR

AF:

0.352

Gnomad4 ASJ

AF:

0.196

Gnomad4 EAS

AF:

0.347

Gnomad4 SAS

AF:

0.271

Gnomad4 FIN

AF:

0.265

Gnomad4 NFE

AF:

0.274

Gnomad4 OTH

AF:

0.282

Alfa

AF:

0.270

Hom.:

8903

Bravo

AF:

0.283

Asia WGS

AF:

0.335

AC:

1163

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Oct 28, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 20163849, 23320911) -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Amelogenesis imperfecta type 1A

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Junctional epidermolysis bullosa gravis of Herlitz

Benign:1

Jul 08, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Junctional epidermolysis bullosa

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

9.4

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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