18-6941663-G-T

Variant names:

• chr18-6941663-G-T
• rs3810046
• NM_005559.4:c.*416C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005559.4(LAMA1):​c.*416C>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 232,064 control chromosomes in the GnomAD database, including 24,291 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 0.43 (15123 hom., cov: 32)
  • Exomes 𝑓: 0.46 (9168 hom.)
• Consequence: LAMA1 NM_005559.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA1	NM_005559.4	c.*416C>A		downstream_gene_variant		ENST00000389658.4	NP_005550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4	c.*416C>A		downstream_gene_variant		1	NM_005559.4	ENSP00000374309.3
LAMA1	ENST00000488064.5	n.*226C>A		downstream_gene_variant		2
LAMA1	ENST00000492048.5	n.*226C>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65530 AN: 151888 Hom.: 15118 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.456 AC: 36512 AN: 80058 Hom.: 9168 AF XY: 0.440 AC XY: 18917 AN XY: 42970

Gnomad4 AFR exome AF: 0.341

Gnomad4 AMR exome AF: 0.276

Gnomad4 ASJ exome AF: 0.488

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.280

Gnomad4 FIN exome AF: 0.554

Gnomad4 NFE exome AF: 0.532

Gnomad4 OTH exome AF: 0.474

GnomAD4 genome AF: 0.431 AC: 65553 AN: 152006 Hom.: 15123 Cov.: 32 AF XY: 0.424 AC XY: 31481 AN XY: 74270

Gnomad4 AFR AF: 0.332

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.524

Gnomad4 OTH AF: 0.422

Alfa AF: 0.487 Hom.: 21168

Bravo AF: 0.409

Asia WGS AF: 0.258 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.0
DANN	Benign	0.56

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3810046; hg19: chr18-6941662;