rs10502349

Variant names:

• chr18-7038140-A-T
• rs10502349
• NM_005559.4:c.1564-389T>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.1564-389T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0903 in 152,220 control chromosomes in the GnomAD database, including 826 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 0.090 (826 hom., cov: 32)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• Publications: 1 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA1	NM_005559.4	c.1564-389T>A		intron_variant	Intron 11 of 62	ENST00000389658.4	NP_005550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4	c.1564-389T>A		intron_variant	Intron 11 of 62	1	NM_005559.4	ENSP00000374309.3
LAMA1	ENST00000579014.5	n.2579-389T>A		intron_variant	Intron 10 of 61	2

Frequencies

GnomAD3 genomes AF: 0.0902 AC: 13723 AN: 152102 Hom.: 820 Cov.: 32

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.0314

Gnomad EAS AF: 0.0431

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0529

Gnomad OTH AF: 0.0866

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

GnomAD4 genome AF: 0.0903 AC: 13751 AN: 152220 Hom.: 826 Cov.: 32 AF XY: 0.0916 AC XY: 6819 AN XY: 74422

African (AFR) AF: 0.153 AC: 6349 AN: 41526

American (AMR) AF: 0.140 AC: 2143 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0314 AC: 109 AN: 3470

East Asian (EAS) AF: 0.0430 AC: 223 AN: 5184

South Asian (SAS) AF: 0.124 AC: 596 AN: 4812

European-Finnish (FIN) AF: 0.0502 AC: 533 AN: 10612

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0530 AC: 3601 AN: 68006

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

Alfa AF: 0.0711 Hom.: 60

Bravo AF: 0.0996

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.4
DANN	Benign	0.86
PhyloP100		-0.085
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: rs10502349; hg19: chr18-7038139;