18-7068463-C-G

Variant names:

• chr18-7068463-C-G
• rs8090011
• NM_005559.4:c.345+11512G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005559.4(LAMA1):​c.345+11512G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 152,126 control chromosomes in the GnomAD database, including 21,322 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 0.50 (21322 hom., cov: 33)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 49 publications found

Genes affected

LAMA1 (HGNC:6481): (laminin subunit alpha 1) This gene encodes one of the alpha 1 subunits of laminin. The laminins are a family of extracellular matrix glycoproteins that have a heterotrimeric structure consisting of an alpha, beta and gamma chain. These proteins make up a major component of the basement membrane and have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Mutations in this gene may be associated with Poretti-Boltshauser syndrome. [provided by RefSeq, Sep 2014]

LAMA1 Gene-Disease associations (from GenCC):

• ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA1	NM_005559.4	c.345+11512G>C		intron_variant	Intron 3 of 62	ENST00000389658.4	NP_005550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4	c.345+11512G>C		intron_variant	Intron 3 of 62	1	NM_005559.4	ENSP00000374309.3
LAMA1	ENST00000579014.5	n.384+11512G>C		intron_variant	Intron 3 of 61	2

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76476 AN: 152006 Hom.: 21271 Cov.: 33

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.410

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.471

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.503 AC: 76592 AN: 152126 Hom.: 21322 Cov.: 33 AF XY: 0.505 AC XY: 37567 AN XY: 74352

African (AFR) AF: 0.739 AC: 30678 AN: 41498

American (AMR) AF: 0.516 AC: 7892 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 975 AN: 3468

East Asian (EAS) AF: 0.704 AC: 3637 AN: 5164

South Asian (SAS) AF: 0.504 AC: 2432 AN: 4826

European-Finnish (FIN) AF: 0.406 AC: 4296 AN: 10576

Middle Eastern (MID) AF: 0.400 AC: 116 AN: 290

European-Non Finnish (NFE) AF: 0.371 AC: 25249 AN: 68002

Other (OTH) AF: 0.476 AC: 1004 AN: 2110

Alfa AF: 0.369 Hom.: 5692

Bravo AF: 0.525

Asia WGS AF: 0.608 AC: 2110 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.041
DANN	Benign	0.46
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs8090011; hg19: chr18-7068462;