18-6996233-G-T

Variant names:

• chr18-6996233-G-T
• rs692849
• NM_005559.4:c.4807-787C>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.4807-787C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 152,042 control chromosomes in the GnomAD database, including 54,012 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 0.84 (54012 hom., cov: 31)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900
• 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, 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LAMA1	NM_005559.4	c.4807-787C>A		intron_variant	Intron 33 of 62	ENST00000389658.4	NP_005550.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LAMA1	ENST00000389658.4	c.4807-787C>A		intron_variant	Intron 33 of 62	1	NM_005559.4	ENSP00000374309.3
LAMA1	ENST00000579014.5	n.5822-787C>A		intron_variant	Intron 32 of 61	2

Frequencies

GnomAD3 genomes AF: 0.839 AC: 127532 AN: 151924 Hom.: 53947 Cov.: 31

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.892

Gnomad SAS AF: 0.875

Gnomad FIN AF: 0.839

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.840 AC: 127659 AN: 152042 Hom.: 54012 Cov.: 31 AF XY: 0.845 AC XY: 62808 AN XY: 74322

African (AFR) AF: 0.939 AC: 38934 AN: 41484

American (AMR) AF: 0.842 AC: 12848 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2501 AN: 3468

East Asian (EAS) AF: 0.892 AC: 4603 AN: 5158

South Asian (SAS) AF: 0.875 AC: 4217 AN: 4818

European-Finnish (FIN) AF: 0.839 AC: 8849 AN: 10546

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53055 AN: 67996

Other (OTH) AF: 0.814 AC: 1712 AN: 2102

Alfa AF: 0.794 Hom.: 88248

Bravo AF: 0.842

Asia WGS AF: 0.872 AC: 3031 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.9
DANN	Benign	0.49
PhyloP100		-0.090
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: rs692849; hg19: chr18-6996232;