NM_198129.4:c.2147+106C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198129.4(LAMA3):​c.2147+106C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000026 in 769,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000026 ( 0 hom. )

Consequence

LAMA3
NM_198129.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0380

Publications

4 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
LAMA3NM_198129.4 linkc.2147+106C>A intron_variant Intron 18 of 74 ENST00000313654.14 NP_937762.2 Q16787-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
LAMA3ENST00000313654.14 linkc.2147+106C>A intron_variant Intron 18 of 74 1 NM_198129.4 ENSP00000324532.8 Q16787-2
LAMA3ENST00000399516.7 linkc.2147+106C>A intron_variant Intron 18 of 73 1 ENSP00000382432.2 Q16787-3A0A0A0MSA0

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000260
AC:
2
AN:
769646
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
403526
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
19880
American (AMR)
AF:
0.00
AC:
0
AN:
35540
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21272
East Asian (EAS)
AF:
0.00
AC:
0
AN:
33294
South Asian (SAS)
AF:
0.00
AC:
0
AN:
67262
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
38532
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
4492
European-Non Finnish (NFE)
AF:
0.00000391
AC:
2
AN:
511628
Other (OTH)
AF:
0.00
AC:
0
AN:
37746
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.67
DANN
Benign
0.34
PhyloP100
-0.038

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

Other links and lift over

dbSNP: rs12608087; hg19: chr18-21396557; API