18-7063197-T-C

Variant summary

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

The NM_005559.4(LAMA1):c.346-12261A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,940 control chromosomes in the GnomAD database, including 11,112 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 0.38 (11112 hom., cov: 32)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA1	NM_005559.4	c.346-12261A>G		intron_variant		ENST00000389658.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA1	ENST00000389658.4	c.346-12261A>G		intron_variant		1	NM_005559.4	P1
LAMA1	ENST00000579014.5	n.385-12261A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57470 AN: 151822 Hom.: 11096 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.379 AC: 57532 AN: 151940 Hom.: 11112 Cov.: 32 AF XY: 0.383 AC XY: 28423 AN XY: 74260

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.458

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.487

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.379

Alfa AF: 0.391 Hom.: 1970

Bravo AF: 0.380

Asia WGS AF: 0.449 AC: 1560 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.85
Dann	Benign	0.55

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: rs10502348; hg19: chr18-7063196;