NM_005559.4:c.6774+504A>T

Variant names:

• chr18-6972553-T-A
• rs17439829
• NM_005559.4:c.6774+504A>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.6774+504A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,266 control chromosomes in the GnomAD database, including 1,088 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 0.11 (1088 hom., cov: 33)
• Consequence: LAMA1 NM_005559.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 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.6774+504A>T		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.6774+504A>T		intron	N/A	ENSP00000374309.3
	LAMA1	ENST00000579014.5	TSL:2	n.7789+504A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17127 AN: 152148 Hom.: 1089 Cov.: 33

Gnomad AFR AF: 0.0479

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.139

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0836

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.113 AC: 17133 AN: 152266 Hom.: 1088 Cov.: 33 AF XY: 0.109 AC XY: 8132 AN XY: 74452

African (AFR) AF: 0.0479 AC: 1990 AN: 41554

American (AMR) AF: 0.139 AC: 2123 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3470

East Asian (EAS) AF: 0.142 AC: 734 AN: 5178

South Asian (SAS) AF: 0.0632 AC: 305 AN: 4824

European-Finnish (FIN) AF: 0.0836 AC: 887 AN: 10616

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.150 AC: 10215 AN: 68010

Other (OTH) AF: 0.117 AC: 247 AN: 2116

Alfa AF: 0.128 Hom.: 169

Bravo AF: 0.116

Asia WGS AF: 0.112 AC: 390 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.61
PhyloP100		0.12
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: rs17439829; hg19: chr18-6972552;