18-6941663-G-T

Variant names:

• chr18-6941663-G-T
• rs3810046
• NM_005559.4:c.*416C>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.*416C>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 232,064 control chromosomes in the GnomAD database, including 24,291 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 0.43 (15123 hom., cov: 32)
  • Exomes 𝑓: 0.46 (9168 hom.)
• Consequence: LAMA1 NM_005559.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.00
• Publications: 8 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, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.519 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA1	NM_005559.4	MANE Select	c.*416C>A		downstream_gene	N/A	NP_005550.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA1	ENST00000389658.4	TSL:1 MANE Select	c.*416C>A		downstream_gene	N/A	ENSP00000374309.3
	LAMA1	ENST00000488064.5	TSL:2	n.*226C>A		downstream_gene	N/A
	LAMA1	ENST00000492048.5	TSL:2	n.*226C>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65530 AN: 151888 Hom.: 15118 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.422

GnomAD4 exome AF: 0.456 AC: 36512 AN: 80058 Hom.: 9168 AF XY: 0.440 AC XY: 18917 AN XY: 42970

African (AFR) AF: 0.341 AC: 633 AN: 1856

American (AMR) AF: 0.276 AC: 1092 AN: 3956

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 904 AN: 1854

East Asian (EAS) AF: 0.203 AC: 790 AN: 3898

South Asian (SAS) AF: 0.280 AC: 3537 AN: 12642

European-Finnish (FIN) AF: 0.554 AC: 2083 AN: 3758

Middle Eastern (MID) AF: 0.426 AC: 110 AN: 258

European-Non Finnish (NFE) AF: 0.532 AC: 25594 AN: 48102

Other (OTH) AF: 0.474 AC: 1769 AN: 3734

GnomAD4 genome AF: 0.431 AC: 65553 AN: 152006 Hom.: 15123 Cov.: 32 AF XY: 0.424 AC XY: 31481 AN XY: 74270

African (AFR) AF: 0.332 AC: 13762 AN: 41460

American (AMR) AF: 0.323 AC: 4928 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1685 AN: 3468

East Asian (EAS) AF: 0.186 AC: 959 AN: 5164

South Asian (SAS) AF: 0.285 AC: 1373 AN: 4814

European-Finnish (FIN) AF: 0.550 AC: 5796 AN: 10542

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.524 AC: 35612 AN: 67970

Other (OTH) AF: 0.422 AC: 892 AN: 2114

Alfa AF: 0.483 Hom.: 55840

Bravo AF: 0.409

Asia WGS AF: 0.258 AC: 899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	4.0
DANN	Benign	0.56
PhyloP100		2.0
Mutation Taster		=95/5	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3810046; hg19: chr18-6941662;