rs475598

Positions:

• chr18-7027439-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.2275-1333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 151,734 control chromosomes in the GnomAD database, including 21,635 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 (21635 hom., cov: 31)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.602

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA1	NM_005559.4	c.2275-1333G>A		intron_variant		ENST00000389658.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA1	ENST00000389658.4	c.2275-1333G>A		intron_variant		1	NM_005559.4	P1
LAMA1	ENST00000579014.5	n.3290-1333G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75471 AN: 151616 Hom.: 21586 Cov.: 31

Gnomad AFR AF: 0.796

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.365

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.498 AC: 75580 AN: 151734 Hom.: 21635 Cov.: 31 AF XY: 0.492 AC XY: 36433 AN XY: 74116

Gnomad4 AFR AF: 0.796

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.470

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.473

Alfa AF: 0.417 Hom.: 6884

Bravo AF: 0.507

Asia WGS AF: 0.281 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.70
DANN	Benign	0.64

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: rs475598; hg19: chr18-7027438;