rs17439829

Positions:

• chr18-6972553-T-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA1	NM_005559.4	c.6774+504A>T		intron_variant		ENST00000389658.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA1	ENST00000389658.4	c.6774+504A>T		intron_variant		1	NM_005559.4	P1
LAMA1	ENST00000579014.5	n.7789+504A>T		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0479

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.0632

Gnomad4 FIN AF: 0.0836

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.117

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs17439829; hg19: chr18-6972552;