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GeneBe

18-23857967-G-C

Variant summary

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

The NM_198129.4(LAMA3):ā€‹c.4260G>Cā€‹(p.Gly1420=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.563 in 1,613,780 control chromosomes in the GnomAD database, including 268,765 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.47 ( 19255 hom., cov: 32)
Exomes š‘“: 0.57 ( 249510 hom. )

Consequence

LAMA3
NM_198129.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.294
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]

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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=-0.78).
BP6
Variant 18-23857967-G-C is Benign according to our data. Variant chr18-23857967-G-C is described in ClinVar as [Benign]. Clinvar id is 403026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-23857967-G-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.294 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/exons MANE UniProt
LAMA3NM_198129.4 linkuse as main transcriptc.4260G>C p.Gly1420= synonymous_variant 33/75 ENST00000313654.14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LAMA3ENST00000313654.14 linkuse as main transcriptc.4260G>C p.Gly1420= synonymous_variant 33/751 NM_198129.4 P1Q16787-2
LAMA3ENST00000399516.7 linkuse as main transcriptc.4260G>C p.Gly1420= synonymous_variant 33/741 Q16787-3
LAMA3ENST00000649721.1 linkuse as main transcriptc.1152G>C p.Gly384= synonymous_variant 8/48

Frequencies

GnomAD3 genomes
AF:
0.475
AC:
72109
AN:
151944
Hom.:
19256
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.258
Gnomad AMI
AF:
0.672
Gnomad AMR
AF:
0.451
Gnomad ASJ
AF:
0.664
Gnomad EAS
AF:
0.161
Gnomad SAS
AF:
0.397
Gnomad FIN
AF:
0.548
Gnomad MID
AF:
0.567
Gnomad NFE
AF:
0.616
Gnomad OTH
AF:
0.513
GnomAD3 exomes
AF:
0.494
AC:
123290
AN:
249472
Hom.:
33728
AF XY:
0.504
AC XY:
68245
AN XY:
135356
show subpopulations
Gnomad AFR exome
AF:
0.247
Gnomad AMR exome
AF:
0.353
Gnomad ASJ exome
AF:
0.664
Gnomad EAS exome
AF:
0.162
Gnomad SAS exome
AF:
0.411
Gnomad FIN exome
AF:
0.554
Gnomad NFE exome
AF:
0.616
Gnomad OTH exome
AF:
0.560
GnomAD4 exome
AF:
0.572
AC:
836700
AN:
1461716
Hom.:
249510
Cov.:
56
AF XY:
0.570
AC XY:
414610
AN XY:
727180
show subpopulations
Gnomad4 AFR exome
AF:
0.245
Gnomad4 AMR exome
AF:
0.366
Gnomad4 ASJ exome
AF:
0.665
Gnomad4 EAS exome
AF:
0.138
Gnomad4 SAS exome
AF:
0.409
Gnomad4 FIN exome
AF:
0.562
Gnomad4 NFE exome
AF:
0.618
Gnomad4 OTH exome
AF:
0.556
GnomAD4 genome
AF:
0.474
AC:
72119
AN:
152064
Hom.:
19255
Cov.:
32
AF XY:
0.466
AC XY:
34615
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.258
Gnomad4 AMR
AF:
0.451
Gnomad4 ASJ
AF:
0.664
Gnomad4 EAS
AF:
0.162
Gnomad4 SAS
AF:
0.397
Gnomad4 FIN
AF:
0.548
Gnomad4 NFE
AF:
0.616
Gnomad4 OTH
AF:
0.509
Alfa
AF:
0.591
Hom.:
8846
Bravo
AF:
0.459
Asia WGS
AF:
0.278
AC:
967
AN:
3478
EpiCase
AF:
0.629
EpiControl
AF:
0.628

ClinVar

Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingInvitaeDec 13, 2023- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 04, 2021- -
not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant 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
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 10, 2021- -
Laryngo-onycho-cutaneous syndrome Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 10, 2021- -
Junctional epidermolysis bullosa gravis of Herlitz Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 10, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
1.9
DANN
Benign
0.63

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.

Other links and lift over

dbSNP: rs867449; hg19: chr18-21437931; COSMIC: COSV58065064; API