18-23816593-C-T

Position:

• chr18-23816593-C-T

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.2147+106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 921,264 control chromosomes in the GnomAD database, including 12,039 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1927 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10112 hom.)
• Consequence: LAMA3 NM_198129.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0380

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 18-23816593-C-T is Benign according to our data. Variant chr18-23816593-C-T is described in ClinVar as [Benign]. Clinvar id is 1274779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LAMA3	NM_198129.4	c.2147+106C>T		intron_variant		ENST00000313654.14	NP_937762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LAMA3	ENST00000313654.14	c.2147+106C>T		intron_variant		1	NM_198129.4	ENSP00000324532.8
LAMA3	ENST00000399516.7	c.2147+106C>T		intron_variant		1		ENSP00000382432.2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19715 AN: 152002 Hom.: 1929 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.113

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.0929

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.0832

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.122 AC: 93639 AN: 769144 Hom.: 10112 AF XY: 0.125 AC XY: 50211 AN XY: 403282

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.568

Gnomad4 SAS exome AF: 0.192

Gnomad4 FIN exome AF: 0.0898

Gnomad4 NFE exome AF: 0.0812

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.130 AC: 19720 AN: 152120 Hom.: 1927 Cov.: 32 AF XY: 0.135 AC XY: 10074 AN XY: 74368

Gnomad4 AFR AF: 0.151

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.113

Gnomad4 EAS AF: 0.567

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.0929

Gnomad4 NFE AF: 0.0832

Gnomad4 OTH AF: 0.154

Alfa AF: 0.0919 Hom.: 1028

Bravo AF: 0.137

Asia WGS AF: 0.353 AC: 1225 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.27

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: rs12608087; hg19: chr18-21396557;