rs16951095

Variant names:

• chr18-7042912-C-T
• rs16951095
• NM_005559.4:c.1155+315G>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.1155+315G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0581 in 293,176 control chromosomes in the GnomAD database, including 760 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 0.056 (355 hom., cov: 32)
  • Exomes 𝑓: 0.060 (405 hom.)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 14 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 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.1155+315G>A		intron	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.1155+315G>A		intron	N/A	ENSP00000374309.3
	LAMA1	ENST00000579014.5	TSL:2	n.1509G>A		non_coding_transcript_exon	Exon 8 of 62

Frequencies

GnomAD3 genomes AF: 0.0560 AC: 8517 AN: 151992 Hom.: 354 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.0823

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0450

Gnomad FIN AF: 0.0547

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0685

Gnomad OTH AF: 0.0528

GnomAD4 exome AF: 0.0604 AC: 8519 AN: 141066 Hom.: 405 Cov.: 0 AF XY: 0.0592 AC XY: 4375 AN XY: 73848

African (AFR) AF: 0.0144 AC: 53 AN: 3668

American (AMR) AF: 0.0790 AC: 445 AN: 5634

Ashkenazi Jewish (ASJ) AF: 0.0365 AC: 163 AN: 4462

East Asian (EAS) AF: 0.167 AC: 1313 AN: 7866

South Asian (SAS) AF: 0.0335 AC: 432 AN: 12884

European-Finnish (FIN) AF: 0.0471 AC: 321 AN: 6820

Middle Eastern (MID) AF: 0.0344 AC: 22 AN: 640

European-Non Finnish (NFE) AF: 0.0586 AC: 5320 AN: 90774

Other (OTH) AF: 0.0541 AC: 450 AN: 8318

GnomAD4 genome AF: 0.0560 AC: 8522 AN: 152110 Hom.: 355 Cov.: 32 AF XY: 0.0579 AC XY: 4304 AN XY: 74364

African (AFR) AF: 0.0148 AC: 613 AN: 41514

American (AMR) AF: 0.0824 AC: 1257 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.0418 AC: 145 AN: 3472

East Asian (EAS) AF: 0.167 AC: 863 AN: 5154

South Asian (SAS) AF: 0.0453 AC: 218 AN: 4816

European-Finnish (FIN) AF: 0.0547 AC: 580 AN: 10602

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0686 AC: 4661 AN: 67980

Other (OTH) AF: 0.0542 AC: 114 AN: 2104

Alfa AF: 0.0673 Hom.: 1184

Bravo AF: 0.0570

Asia WGS AF: 0.109 AC: 380 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.2
DANN	Benign	0.74
PhyloP100		-0.20
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: rs16951095; hg19: chr18-7042911; COSMIC: COSV67531192;