rs7231835

chr18-7034272-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.2051+207G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 152,086 control chromosomes in the GnomAD database, including 6,551 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 0.26 (6551 hom., cov: 33)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.550

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA1	NM_005559.4	c.2051+207G>A		intron_variant		ENST00000389658.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA1	ENST00000389658.4	c.2051+207G>A		intron_variant		1	NM_005559.4	P1
LAMA1	ENST00000579014.5	n.3066+207G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.256 AC: 38849 AN: 151968 Hom.: 6544 Cov.: 33

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.256 AC: 38898 AN: 152086 Hom.: 6551 Cov.: 33 AF XY: 0.252 AC XY: 18700 AN XY: 74346

Gnomad4 AFR AF: 0.483

Gnomad4 AMR AF: 0.169

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.0320

Gnomad4 SAS AF: 0.176

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.210

Alfa AF: 0.191 Hom.: 1816

Bravo AF: 0.260

Asia WGS AF: 0.155 AC: 538 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.5
Dann	Benign	0.66

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: rs7231835; hg19: chr18-7034271;