rs16951095

Positions:

• chr18-7042912-C-T

Variant summary

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

The NM_005559.4(LAMA1):​c.1155+315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 293,176 control chromosomes in the GnomAD database, including 760 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 0.056 (355 hom., cov: 32)
  • Exomes 𝑓: 0.060 (405 hom.)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA1	NM_005559.4	c.1155+315G>A		intron_variant		ENST00000389658.4	NP_005550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4	c.1155+315G>A		intron_variant		1	NM_005559.4	ENSP00000374309	P1
LAMA1	ENST00000579014.5	n.1509G>A		non_coding_transcript_exon_variant	8/62	2

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8517 AN: 151992 Hom.: 354 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0685

Gnomad OTH AF: 0.0528

GnomAD4 exome AF: 0.0604 AC: 8519 AN: 141066 Hom.: 405 Cov.: 0 AF XY: 0.0592 AC XY: 4375 AN XY: 73848

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.0790

Gnomad4 ASJ exome AF: 0.0365

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.0335

Gnomad4 FIN exome AF: 0.0471

Gnomad4 NFE exome AF: 0.0586

Gnomad4 OTH exome AF: 0.0541

GnomAD4 genome AF: 0.0560 AC: 8522 AN: 152110 Hom.: 355 Cov.: 32 AF XY: 0.0579 AC XY: 4304 AN XY: 74364

Gnomad4 AFR AF: 0.0148

Gnomad4 AMR AF: 0.0824

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.0453

Gnomad4 FIN AF: 0.0547

Gnomad4 NFE AF: 0.0686

Gnomad4 OTH AF: 0.0542

Alfa AF: 0.0688 Hom.: 787

Bravo AF: 0.0570

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.74

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

Other links and lift over

dbSNP: rs16951095; hg19: chr18-7042911; COSMIC: COSV67531192; COSMIC: COSV67531192;