rs2282854

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001105206.3(LAMA4):​c.298-3314A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0616 in 152,248 control chromosomes in the GnomAD database, including 340 homozygotes. 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: 𝑓 0.062 ( 340 hom., cov: 32)

Consequence

LAMA4
NM_001105206.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.671
Variant links:
Genes affected
LAMA4 (HGNC:6484): (laminin subunit alpha 4) Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene. Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the alpha chain isoform laminin, alpha 4. The domain structure of alpha 4 is similar to that of alpha 3, both of which resemble truncated versions of alpha 1 and alpha 2, in that approximately 1,200 residues at the N-terminus (domains IV, V and VI) have been lost. Laminin, alpha 4 contains the C-terminal G domain which distinguishes all alpha chains from the beta and gamma chains. The RNA analysis from adult and fetal tissues revealed developmental regulation of expression, however, the exact function of laminin, alpha 4 is not known. Tissue-specific utilization of alternative polyA-signal has been described in literature. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
LAMA4NM_001105206.3 linkuse as main transcriptc.298-3314A>G intron_variant ENST00000230538.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
LAMA4ENST00000230538.12 linkuse as main transcriptc.298-3314A>G intron_variant 1 NM_001105206.3 A1

Frequencies

GnomAD3 genomes
AF:
0.0617
AC:
9384
AN:
152130
Hom.:
342
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0415
Gnomad AMI
AF:
0.152
Gnomad AMR
AF:
0.0908
Gnomad ASJ
AF:
0.121
Gnomad EAS
AF:
0.149
Gnomad SAS
AF:
0.0965
Gnomad FIN
AF:
0.0236
Gnomad MID
AF:
0.120
Gnomad NFE
AF:
0.0590
Gnomad OTH
AF:
0.0865
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0616
AC:
9378
AN:
152248
Hom.:
340
Cov.:
32
AF XY:
0.0621
AC XY:
4621
AN XY:
74446
show subpopulations
Gnomad4 AFR
AF:
0.0414
Gnomad4 AMR
AF:
0.0907
Gnomad4 ASJ
AF:
0.121
Gnomad4 EAS
AF:
0.149
Gnomad4 SAS
AF:
0.0968
Gnomad4 FIN
AF:
0.0236
Gnomad4 NFE
AF:
0.0590
Gnomad4 OTH
AF:
0.0842
Alfa
AF:
0.0650
Hom.:
648
Bravo
AF:
0.0640
Asia WGS
AF:
0.118
AC:
410
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
4.1
DANN
Benign
0.40

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: rs2282854; hg19: chr6-112531660; API