1-209628174-C-T

Position:

chr1-209628174-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000228.3(LAMB3):c.1149G>A(p.Pro383=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0225 in 1,561,816 control chromosomes in the GnomAD database, including 2,908 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P383P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.059 ( 639 hom., cov: 33)

Exomes 𝑓: 0.019 ( 2269 hom. )

Consequence

LAMB3
NM_000228.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.90

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 -21 ACMG points.

BP4

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

BP6

Variant 1-209628174-C-T is Benign according to our data. Variant chr1-209628174-C-T is described in ClinVar as [Benign]. Clinvar id is 255582.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-209628174-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.9 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.247 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.1149G>A	p.Pro383=	synonymous_variant	11/23	ENST00000356082.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
LAMB3	ENST00000356082.9 linkuse as main transcript	c.1149G>A	p.Pro383=	synonymous_variant	11/23	1	NM_000228.3	P1
LAMB3	ENST00000367030.7 linkuse as main transcript	c.1149G>A	p.Pro383=	synonymous_variant	11/23	1		P1
LAMB3	ENST00000391911.5 linkuse as main transcript	c.1149G>A	p.Pro383=	synonymous_variant	10/22	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0585

AC:

8897

AN:

152130

Hom.:

629

Cov.:

show subpopulations

Gnomad AFR

AF:

0.127

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.257

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.0602

GnomAD3 exomes

AF:

0.0611

AC:

10304

AN:

168724

Hom.:

988

AF XY:

0.0519

AC XY:

4642

AN XY:

89478

show subpopulations

Gnomad AFR exome

AF:

0.131

Gnomad AMR exome

AF:

0.188

Gnomad ASJ exome

AF:

0.00231

Gnomad EAS exome

AF:

0.264

Gnomad SAS exome

AF:

0.0146

Gnomad FIN exome

AF:

0.00477

Gnomad NFE exome

AF:

0.00348

Gnomad OTH exome

AF:

0.0423

GnomAD4 exome

AF:

0.0185

AC:

26146

AN:

1409566

Hom.:

2269

Cov.:

AF XY:

0.0175

AC XY:

12209

AN XY:

696344

show subpopulations

Gnomad4 AFR exome

AF:

0.137

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.00249

Gnomad4 EAS exome

AF:

0.257

Gnomad4 SAS exome

AF:

0.0150

Gnomad4 FIN exome

AF:

0.00468

Gnomad4 NFE exome

AF:

0.00191

Gnomad4 OTH exome

AF:

0.0322

GnomAD4 genome

AF:

0.0587

AC:

8944

AN:

152250

Hom.:

639

Cov.:

AF XY:

0.0604

AC XY:

4499

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.127

Gnomad4 AMR

AF:

0.119

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.258

Gnomad4 SAS

AF:

0.0180

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.0629

Alfa

AF:

0.0176

Hom.:

336

Bravo

AF:

0.0748

Asia WGS

AF:

0.139

AC:

481

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 12, 2021	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Junctional epidermolysis bullosa

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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

-0.75

CADD

Benign

2.1

DANN

Benign

0.85

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