rs117044923

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198129.4(LAMA3):c.294+47G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 1,330,512 control chromosomes in the GnomAD database, including 1,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 432 hom., cov: 32)

Exomes 𝑓: 0.026 ( 1076 hom. )

Consequence

LAMA3
NM_198129.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.544

Publications

0 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: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
junctional epidermolysis bullosa Herlitz type
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
junctional epidermolysis bullosa, non-Herlitz type
Inheritance: AR Classification: STRONG Submitted by: 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 -20 ACMG points.

BP4

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

BP6

Variant 18-23690024-G-T is Benign according to our data. Variant chr18-23690024-G-T is described in ClinVar as Benign. ClinVar VariationId is 1238740.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LAMA3	NM_198129.4	MANE Select	c.294+47G>T	intron	N/A	NP_937762.2	Q16787-2
LAMA3	NM_001127717.4		c.294+47G>T	intron	N/A	NP_001121189.2	A0A0A0MSA0
LAMA3	NM_001302996.2		c.294+47G>T	intron	N/A	NP_001289925.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
LAMA3	ENST00000313654.14	TSL:1 MANE Select	c.294+47G>T	intron	N/A	ENSP00000324532.8	Q16787-2
LAMA3	ENST00000399516.7	TSL:1	c.294+47G>T	intron	N/A	ENSP00000382432.2	Q16787-3
LAMA3	ENST00000585600.5	TSL:1	n.294+47G>T	intron	N/A	ENSP00000468316.1	A0A075B783

Frequencies

GnomAD3 genomes

AF:

0.0476

AC:

7235

AN:

152116

Hom.:

425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0579

Gnomad AMI

AF:

0.119

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.0112

Gnomad EAS

AF:

0.0776

Gnomad SAS

AF:

0.0743

Gnomad FIN

AF:

0.00867

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0401

GnomAD2 exomes

AF:

0.101

AC:

2351

AN:

23392

AF XY:

0.0882

show subpopulations

Gnomad AFR exome

AF:

0.0588

Gnomad AMR exome

AF:

0.249

Gnomad ASJ exome

AF:

0.0187

Gnomad EAS exome

AF:

0.0766

Gnomad FIN exome

AF:

0.0101

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.0628

GnomAD4 exome

AF:

0.0257

AC:

30324

AN:

1178278

Hom.:

1076

Cov.:

AF XY:

0.0267

AC XY:

15297

AN XY:

571892

show subpopulations

African (AFR)

AF:

0.0596

AC:

1392

AN:

23366

American (AMR)

AF:

0.220

AC:

3718

AN:

16868

Ashkenazi Jewish (ASJ)

AF:

0.0154

AC:

270

AN:

17566

East Asian (EAS)

AF:

0.0911

AC:

2584

AN:

28376

South Asian (SAS)

AF:

0.0777

AC:

4374

AN:

56272

European-Finnish (FIN)

AF:

0.0123

AC:

390

AN:

31804

Middle Eastern (MID)

AF:

0.0182

AC:

AN:

3800

European-Non Finnish (NFE)

AF:

0.0168

AC:

15963

AN:

950576

Other (OTH)

AF:

0.0315

AC:

1564

AN:

49650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1414

2827

4241

5654

7068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

742

1484

2226

2968

3710

<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:

0.0477

AC:

7257

AN:

152234

Hom.:

432

Cov.:

AF XY:

0.0512

AC XY:

3815

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.0579

AC:

2405

AN:

41548

American (AMR)

AF:

0.174

AC:

2654

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

AN:

3472

East Asian (EAS)

AF:

0.0775

AC:

400

AN:

5158

South Asian (SAS)

AF:

0.0752

AC:

363

AN:

4828

European-Finnish (FIN)

AF:

0.00867

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0162

AC:

1101

AN:

68004

Other (OTH)

AF:

0.0406

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

328

656

985

1313

1641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

156

234

312

390

<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:

0.0334

Hom.:

Bravo

AF:

0.0611

Asia WGS

AF:

0.0790

AC:

273

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

(source)

DANN

Benign

0.89

PhyloP100

-0.54

PromoterAI

0.033

Neutral

(source)

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over