rs600695

Variant names:

• chr18-7034947-G-A
• rs600695
• NM_005559.4:c.1840-257C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005559.4(LAMA1):​c.1840-257C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,144 control chromosomes in the GnomAD database, including 31,101 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 0.62 (31101 hom., cov: 32)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135
• Publications: 2 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA1	NM_005559.4	c.1840-257C>T		intron_variant	Intron 13 of 62	ENST00000389658.4	NP_005550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4	c.1840-257C>T		intron_variant	Intron 13 of 62	1	NM_005559.4	ENSP00000374309.3
LAMA1	ENST00000579014.5	n.2855-257C>T		intron_variant	Intron 12 of 61	2

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93815 AN: 152026 Hom.: 31045 Cov.: 32

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.459

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.710

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.617 AC: 93934 AN: 152144 Hom.: 31101 Cov.: 32 AF XY: 0.614 AC XY: 45645 AN XY: 74388

African (AFR) AF: 0.854 AC: 35497 AN: 41554

American (AMR) AF: 0.459 AC: 7017 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1994 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1156 AN: 5160

South Asian (SAS) AF: 0.466 AC: 2248 AN: 4822

European-Finnish (FIN) AF: 0.629 AC: 6647 AN: 10560

Middle Eastern (MID) AF: 0.709 AC: 207 AN: 292

European-Non Finnish (NFE) AF: 0.552 AC: 37510 AN: 67988

Other (OTH) AF: 0.600 AC: 1263 AN: 2106

Alfa AF: 0.560 Hom.: 44876

Bravo AF: 0.613

Asia WGS AF: 0.396 AC: 1379 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.2
DANN	Benign	0.81
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs600695; hg19: chr18-7034946;