18-23933804-C-T

Position:

chr18-23933804-C-T

Variant summary

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

The NM_198129.4(LAMA3):c.8731C>T(p.Leu2911=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 1,613,476 control chromosomes in the GnomAD database, including 32,634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2284 hom., cov: 33)

Exomes 𝑓: 0.20 ( 30350 hom. )

Consequence

LAMA3
NM_198129.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: 0.542

Variant links:

Genes affected

LAMA3 (HGNC:6483): (laminin subunit alpha 3) The protein encoded by this gene belongs to the laminin family of secreted molecules. Laminins are heterotrimeric molecules that consist of alpha, beta, and gamma subunits that assemble through a coiled-coil domain. Laminins are essential for formation and function of the basement membrane and have additional functions in regulating cell migration and mechanical signal transduction. This gene encodes an alpha subunit and is responsive to several epithelial-mesenchymal regulators including keratinocyte growth factor, epidermal growth factor and insulin-like growth factor. Mutations in this gene have been identified as the cause of Herlitz type junctional epidermolysis bullosa and laryngoonychocutaneous syndrome. Alternative splicing and alternative promoter usage result in multiple transcript variants. [provided by RefSeq, Dec 2014]

LAMA3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 18-23933804-C-T is Benign according to our data. Variant chr18-23933804-C-T is described in ClinVar as [Benign]. Clinvar id is 255578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.542 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA3	NM_198129.4 linkuse as main transcript	c.8731C>T	p.Leu2911=	synonymous_variant	67/75	ENST00000313654.14
LAMA3	NM_000227.6 linkuse as main transcript	c.3904C>T	p.Leu1302=	synonymous_variant	30/38	ENST00000269217.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA3	ENST00000313654.14 linkuse as main transcript	c.8731C>T	p.Leu2911=	synonymous_variant	67/75	1	NM_198129.4	P1	Q16787-2
LAMA3	ENST00000269217.11 linkuse as main transcript	c.3904C>T	p.Leu1302=	synonymous_variant	30/38	1	NM_000227.6		Q16787-1

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23694

AN:

152142

Hom.:

2277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0425

Gnomad AMI

AF:

0.0811

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.167

Gnomad SAS

AF:

0.238

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.207

Gnomad OTH

AF:

0.149

GnomAD3 exomes

AF:

0.190

AC:

47764

AN:

251310

Hom.:

4978

AF XY:

0.194

AC XY:

26385

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0349

Gnomad AMR exome

AF:

0.174

Gnomad ASJ exome

AF:

0.139

Gnomad EAS exome

AF:

0.166

Gnomad SAS exome

AF:

0.237

Gnomad FIN exome

AF:

0.245

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.183

GnomAD4 exome

AF:

0.201

AC:

293494

AN:

1461216

Hom.:

30350

Cov.:

AF XY:

0.202

AC XY:

146768

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.0306

Gnomad4 AMR exome

AF:

0.174

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.180

Gnomad4 SAS exome

AF:

0.238

Gnomad4 FIN exome

AF:

0.238

Gnomad4 NFE exome

AF:

0.206

Gnomad4 OTH exome

AF:

0.181

GnomAD4 genome

AF:

0.156

AC:

23709

AN:

152260

Hom.:

2284

Cov.:

AF XY:

0.158

AC XY:

11734

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0423

Gnomad4 AMR

AF:

0.148

Gnomad4 ASJ

AF:

0.144

Gnomad4 EAS

AF:

0.168

Gnomad4 SAS

AF:

0.237

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.207

Gnomad4 OTH

AF:

0.155

Alfa

AF:

0.186

Hom.:

5585

Bravo

AF:

0.140

Asia WGS

AF:

0.210

AC:

732

AN:

3478

EpiCase

AF:

0.190

EpiControl

AF:

0.186

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Laryngo-onycho-cutaneous syndrome

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

Junctional epidermolysis bullosa gravis of Herlitz

Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.3

DANN

Benign

0.82

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