chr18-7063197-T-C

Variant names:

• chr18-7063197-T-C
• rs10502348
• NM_005559.4:c.346-12261A>G

Variant summary

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

The NM_005559.4(LAMA1):​c.346-12261A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,940 control chromosomes in the GnomAD database, including 11,112 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 0.38 (11112 hom., cov: 32)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.471 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.346-12261A>G		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.346-12261A>G		intron	N/A	ENSP00000374309.3	P25391
	LAMA1	ENST00000940203.1		c.346-12261A>G		intron	N/A	ENSP00000610262.1
	LAMA1	ENST00000940200.1		c.346-12261A>G		intron	N/A	ENSP00000610259.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57470 AN: 151822 Hom.: 11096 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.485

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.379 AC: 57532 AN: 151940 Hom.: 11112 Cov.: 32 AF XY: 0.383 AC XY: 28423 AN XY: 74260

African (AFR) AF: 0.320 AC: 13277 AN: 41452

American (AMR) AF: 0.458 AC: 6995 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 998 AN: 3470

East Asian (EAS) AF: 0.447 AC: 2296 AN: 5140

South Asian (SAS) AF: 0.487 AC: 2337 AN: 4796

European-Finnish (FIN) AF: 0.412 AC: 4347 AN: 10560

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.384 AC: 26070 AN: 67952

Other (OTH) AF: 0.379 AC: 798 AN: 2104

Alfa AF: 0.391 Hom.: 1970

Bravo AF: 0.380

Asia WGS AF: 0.449 AC: 1560 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.85
DANN	Benign	0.55
PhyloP100		-0.69
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: rs10502348; hg19: chr18-7063196;