18-23690024-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198129.4(LAMA3):c.294+47G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0282 in 1,330,512 control chromosomes in the GnomAD database, including 1,508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.048 (432 hom., cov: 32)
  • Exomes 𝑓: 0.026 (1076 hom.)
• Consequence: LAMA3 NM_198129.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.544

Genes affected

LAMA3 (HGNC:6483): (laminin subunit alpha 3) The protein encoded by this gene belongs to the laminin family of secreted molecules. Laminins are heterotrimeric molecules that consist of alpha, beta, and gamma subunits that assemble through a coiled-coil domain. Laminins are essential for formation and function of the basement membrane and have additional functions in regulating cell migration and mechanical signal transduction. This gene encodes an alpha subunit and is responsive to several epithelial-mesenchymal regulators including keratinocyte growth factor, epidermal growth factor and insulin-like growth factor. Mutations in this gene have been identified as the cause of Herlitz type junctional epidermolysis bullosa and laryngoonychocutaneous syndrome. Alternative splicing and alternative promoter usage result in multiple transcript variants. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 18-23690024-G-T is Benign according to our data. Variant chr18-23690024-G-T is described in ClinVar as [Benign]. Clinvar id is 1238740.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA3	NM_198129.4	c.294+47G>T		intron_variant		ENST00000313654.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA3	ENST00000313654.14	c.294+47G>T		intron_variant		1	NM_198129.4	P1
LAMA3	ENST00000399516.7	c.294+47G>T		intron_variant		1
LAMA3	ENST00000585600.5	c.294+47G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0476 AC: 7235 AN: 152116 Hom.: 425 Cov.: 32

Gnomad AFR AF: 0.0579

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.0776

Gnomad SAS AF: 0.0743

Gnomad FIN AF: 0.00867

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0162

Gnomad OTH AF: 0.0401

GnomAD3 exomes AF: 0.101 AC: 2351 AN: 23392 Hom.: 273 AF XY: 0.0882 AC XY: 1067 AN XY: 12096

Gnomad AFR exome AF: 0.0588

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.0187

Gnomad EAS exome AF: 0.0766

Gnomad SAS exome AF: 0.0706

Gnomad FIN exome AF: 0.0101

Gnomad NFE exome AF: 0.0153

Gnomad OTH exome AF: 0.0628

GnomAD4 exome AF: 0.0257 AC: 30324 AN: 1178278 Hom.: 1076 Cov.: 18 AF XY: 0.0267 AC XY: 15297 AN XY: 571892

Gnomad4 AFR exome AF: 0.0596

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.0154

Gnomad4 EAS exome AF: 0.0911

Gnomad4 SAS exome AF: 0.0777

Gnomad4 FIN exome AF: 0.0123

Gnomad4 NFE exome AF: 0.0168

Gnomad4 OTH exome AF: 0.0315

GnomAD4 genome AF: 0.0477 AC: 7257 AN: 152234 Hom.: 432 Cov.: 32 AF XY: 0.0512 AC XY: 3815 AN XY: 74444

Gnomad4 AFR AF: 0.0579

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.0775

Gnomad4 SAS AF: 0.0752

Gnomad4 FIN AF: 0.00867

Gnomad4 NFE AF: 0.0162

Gnomad4 OTH AF: 0.0406

Alfa AF: 0.0319 Hom.: 27

Bravo AF: 0.0611

Asia WGS AF: 0.0790 AC: 273 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	2.7
Dann	Benign	0.89

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: rs117044923; hg19: chr18-21269988; COSMIC: COSV58070806;