rs475598

Variant names:

• chr18-7027439-C-T
• rs475598
• NM_005559.4:c.2275-1333G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

LAMA1 Gene-Disease associations (from GenCC):

• ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005559.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA1	NM_005559.4	MANE Select	c.2275-1333G>A		intron	N/A	NP_005550.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA1	ENST00000389658.4	TSL:1 MANE Select	c.2275-1333G>A		intron	N/A	ENSP00000374309.3	P25391
	LAMA1	ENST00000940203.1		c.2275-459G>A		intron	N/A	ENSP00000610262.1
	LAMA1	ENST00000940200.1		c.2275-1333G>A		intron	N/A	ENSP00000610259.1

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

African (AFR) AF: 0.796 AC: 32944 AN: 41380

American (AMR) AF: 0.365 AC: 5561 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3470

East Asian (EAS) AF: 0.167 AC: 859 AN: 5152

South Asian (SAS) AF: 0.298 AC: 1434 AN: 4810

European-Finnish (FIN) AF: 0.429 AC: 4476 AN: 10434

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27282 AN: 67926

Other (OTH) AF: 0.473 AC: 1000 AN: 2112

Alfa AF: 0.421 Hom.: 7838

Bravo AF: 0.507

Asia WGS AF: 0.281 AC: 975 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.70
DANN	Benign	0.64
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs475598; hg19: chr18-7027438;