18-23833905-T-C

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.2901T>C(p.Ala967Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.685 in 1,613,790 control chromosomes in the GnomAD database, including 381,236 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.64 ( 31991 hom., cov: 32)

Exomes 𝑓: 0.69 ( 349245 hom. )

Consequence

LAMA3
NM_198129.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.667

Publications

23 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=-0.9).

BP6

Variant 18-23833905-T-C is Benign according to our data. Variant chr18-23833905-T-C is described in ClinVar as Benign. ClinVar VariationId is 403025.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.667 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198129.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA3	NM_198129.4	MANE Select	c.2901T>C	p.Ala967Ala	synonymous	Exon 24 of 75	NP_937762.2
	LAMA3	NM_001127717.4		c.2901T>C	p.Ala967Ala	synonymous	Exon 24 of 74	NP_001121189.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LAMA3	ENST00000313654.14	TSL:1 MANE Select	c.2901T>C	p.Ala967Ala	synonymous	Exon 24 of 75	ENSP00000324532.8
LAMA3	ENST00000399516.7	TSL:1	c.2901T>C	p.Ala967Ala	synonymous	Exon 24 of 74	ENSP00000382432.2
LAMA3	ENST00000591749.1	TSL:4	n.142T>C		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.644

AC:

97859

AN:

151888

Hom.:

31988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.538

Gnomad AMI

AF:

0.770

Gnomad AMR

AF:

0.602

Gnomad ASJ

AF:

0.776

Gnomad EAS

AF:

0.754

Gnomad SAS

AF:

0.626

Gnomad FIN

AF:

0.640

Gnomad MID

AF:

0.791

Gnomad NFE

AF:

0.701

Gnomad OTH

AF:

0.709

GnomAD2 exomes

AF:

0.660

AC:

164624

AN:

249526

AF XY:

0.666

show subpopulations

Gnomad AFR exome

AF:

0.534

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.781

Gnomad EAS exome

AF:

0.764

Gnomad FIN exome

AF:

0.651

Gnomad NFE exome

AF:

0.703

Gnomad OTH exome

AF:

0.697

GnomAD4 exome

AF:

0.689

AC:

1007421

AN:

1461784

Hom.:

349245

Cov.:

AF XY:

0.689

AC XY:

500865

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.541

AC:

18102

AN:

33474

American (AMR)

AF:

0.529

AC:

23648

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.780

AC:

20390

AN:

26136

East Asian (EAS)

AF:

0.737

AC:

29268

AN:

39698

South Asian (SAS)

AF:

0.619

AC:

53425

AN:

86254

European-Finnish (FIN)

AF:

0.655

AC:

34968

AN:

53416

Middle Eastern (MID)

AF:

0.781

AC:

4477

AN:

5736

European-Non Finnish (NFE)

AF:

0.702

AC:

780863

AN:

1111956

Other (OTH)

AF:

0.700

AC:

42280

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

19091

38183

57274

76366

95457

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19598

39196

58794

78392

97990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.644

AC:

97906

AN:

152006

Hom.:

31991

Cov.:

AF XY:

0.641

AC XY:

47639

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.538

AC:

22311

AN:

41440

American (AMR)

AF:

0.602

AC:

9196

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.776

AC:

2694

AN:

3470

East Asian (EAS)

AF:

0.754

AC:

3889

AN:

5158

South Asian (SAS)

AF:

0.626

AC:

3013

AN:

4814

European-Finnish (FIN)

AF:

0.640

AC:

6755

AN:

10550

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.701

AC:

47633

AN:

67978

Other (OTH)

AF:

0.703

AC:

1485

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1772

3544

5317

7089

8861

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

788

1576

2364

3152

3940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.682

Hom.:

19423

Bravo

AF:

0.640

Asia WGS

AF:

0.654

AC:

2276

AN:

3478

EpiCase

AF:

0.717

EpiControl

AF:

0.722

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

Nov 12, 2018

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.3

(source)

DANN

Benign

0.45

PhyloP100

-0.67

PromoterAI

0.0080

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over