18-23861753-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_198129.4(LAMA3):c.4530C>T(p.Pro1510Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,612,978 control chromosomes in the GnomAD database, including 267,823 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 19028 hom., cov: 32)

Exomes 𝑓: 0.57 ( 248795 hom. )

Consequence

LAMA3
NM_198129.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.50

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

junctional epidermolysis bullosa
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
laryngo-onycho-cutaneous syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
junctional epidermolysis bullosa Herlitz type
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
junctional epidermolysis bullosa, non-Herlitz type
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp
generalized junctional epidermolysis bullosa non-Herlitz type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LAMA3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 18-23861753-C-T is Benign according to our data. Variant chr18-23861753-C-T is described in ClinVar as [Benign]. Clinvar id is 403027.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA3	NM_198129.4 link	c.4530C>T	p.Pro1510Pro	synonymous_variant	Exon 35 of 75	ENST00000313654.14	NP_937762.2	Q16787-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
LAMA3	ENST00000313654.14 link	c.4530C>T	p.Pro1510Pro	synonymous_variant	Exon 35 of 75	1	NM_198129.4	ENSP00000324532.8	Q16787-2
LAMA3	ENST00000399516.7 link	c.4530C>T	p.Pro1510Pro	synonymous_variant	Exon 35 of 74	1		ENSP00000382432.2	Q16787-3A0A0A0MSA0
LAMA3	ENST00000649721.1 link	c.1422C>T	p.Pro474Pro	synonymous_variant	Exon 10 of 48			ENSP00000497885.1	A0A3B3ITG1

Frequencies

GnomAD3 genomes

AF:

0.470

AC:

71339

AN:

151876

Hom.:

19029

Cov.:

show subpopulations

Gnomad AFR

AF:

0.242

Gnomad AMI

AF:

0.671

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.659

Gnomad EAS

AF:

0.161

Gnomad SAS

AF:

0.397

Gnomad FIN

AF:

0.548

Gnomad MID

AF:

0.566

Gnomad NFE

AF:

0.616

Gnomad OTH

AF:

0.508

GnomAD2 exomes

AF:

0.492

AC:

121982

AN:

247702

AF XY:

0.502

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.659

Gnomad EAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.555

Gnomad NFE exome

AF:

0.616

Gnomad OTH exome

AF:

0.557

GnomAD4 exome

AF:

0.572

AC:

835050

AN:

1460982

Hom.:

248795

Cov.:

AF XY:

0.569

AC XY:

413799

AN XY:

726726

show subpopulations

African (AFR)

AF:

0.229

AC:

7675

AN:

33470

American (AMR)

AF:

0.364

AC:

16245

AN:

44616

Ashkenazi Jewish (ASJ)

AF:

0.661

AC:

17274

AN:

26132

East Asian (EAS)

AF:

0.138

AC:

5467

AN:

39674

South Asian (SAS)

AF:

0.409

AC:

35205

AN:

86164

European-Finnish (FIN)

AF:

0.562

AC:

29969

AN:

53330

Middle Eastern (MID)

AF:

0.581

AC:

3346

AN:

5762

European-Non Finnish (NFE)

AF:

0.618

AC:

686455

AN:

1111462

Other (OTH)

AF:

0.553

AC:

33414

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

18140

36280

54420

72560

90700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.469

AC:

71346

AN:

151996

Hom.:

19028

Cov.:

AF XY:

0.461

AC XY:

34255

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.242

AC:

10028

AN:

41446

American (AMR)

AF:

0.447

AC:

6825

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.659

AC:

2288

AN:

3470

East Asian (EAS)

AF:

0.162

AC:

837

AN:

5170

South Asian (SAS)

AF:

0.397

AC:

1910

AN:

4810

European-Finnish (FIN)

AF:

0.548

AC:

5786

AN:

10564

Middle Eastern (MID)

AF:

0.575

AC:

169

AN:

294

European-Non Finnish (NFE)

AF:

0.616

AC:

41835

AN:

67958

Other (OTH)

AF:

0.503

AC:

1059

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1737

3474

5212

6949

8686

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.577

Hom.:

57572

Bravo

AF:

0.453

Asia WGS

AF:

0.275

AC:

957

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

Dec 13, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 28, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

Junctional epidermolysis bullosa, non-Herlitz type

Benign:1

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Laryngo-onycho-cutaneous syndrome

Benign:1

Jul 10, 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 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.39

(source)

DANN

Benign

0.46

PhyloP100

-2.5

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

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18-23861753-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over