chr18-23901376-A-G

Position:

• chr18-23901376-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_198129.4(LAMA3):​c.6201+53A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 1,451,370 control chromosomes in the GnomAD database, including 106,814 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10584 hom., cov: 32)
  • Exomes 𝑓: 0.38 (96230 hom.)
• Consequence: LAMA3 NM_198129.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.623

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]

LAMA3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 18-23901376-A-G is Benign according to our data. Variant chr18-23901376-A-G is described in ClinVar as [Benign]. Clinvar id is 1184664.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA3	NM_198129.4	c.6201+53A>G		intron_variant		ENST00000313654.14	NP_937762.2
LAMA3	NM_000227.6	c.1374+53A>G		intron_variant		ENST00000269217.11	NP_000218.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA3	ENST00000313654.14	c.6201+53A>G		intron_variant		1	NM_198129.4	ENSP00000324532.8
LAMA3	ENST00000269217.11	c.1374+53A>G		intron_variant		1	NM_000227.6	ENSP00000269217.5

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55262 AN: 151890 Hom.: 10578 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.377

GnomAD4 exome AF: 0.375 AC: 487328 AN: 1299362 Hom.: 96230 AF XY: 0.378 AC XY: 247111 AN XY: 654478

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.360

Gnomad4 ASJ exome AF: 0.308

Gnomad4 EAS exome AF: 0.791

Gnomad4 SAS exome AF: 0.451

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.355

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.364 AC: 55288 AN: 152008 Hom.: 10584 Cov.: 32 AF XY: 0.371 AC XY: 27531 AN XY: 74296

Gnomad4 AFR AF: 0.307

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.459

Gnomad4 FIN AF: 0.424

Gnomad4 NFE AF: 0.360

Gnomad4 OTH AF: 0.382

Alfa AF: 0.336 Hom.: 19693

Bravo AF: 0.355

Asia WGS AF: 0.590 AC: 2052 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Junctional epidermolysis bullosa, non-Herlitz type Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Laryngo-onycho-cutaneous syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Junctional epidermolysis bullosa gravis of Herlitz Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	1.3
DANN	Benign	0.78

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: rs1154227; hg19: chr18-21481340;