Variant 18-23946123-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198129.4(LAMA3):c.9211-21C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 1,607,248 control chromosomes in the GnomAD database, including 317,497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 22805 hom., cov: 30)

Exomes 𝑓: 0.62 ( 294692 hom. )

Consequence

LAMA3
NM_198129.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.09

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 18-23946123-C-T is Benign according to our data. Variant chr18-23946123-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 255579.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA3	NM_000227.6 linkuse as main transcript	c.4384-21C>T		intron_variant		ENST00000269217.11
LAMA3	NM_198129.4 linkuse as main transcript	c.9211-21C>T		intron_variant		ENST00000313654.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA3	ENST00000269217.11 linkuse as main transcript	c.4384-21C>T		intron_variant		1	NM_000227.6		Q16787-1
LAMA3	ENST00000313654.14 linkuse as main transcript	c.9211-21C>T		intron_variant		1	NM_198129.4	P1	Q16787-2

Frequencies

GnomAD3 genomes

AF:

0.514

AC:

78049

AN:

151742

Hom.:

22806

Cov.:

show subpopulations

Gnomad AFR

AF:

0.268

Gnomad AMI

AF:

0.707

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.704

Gnomad EAS

AF:

0.162

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.627

Gnomad MID

AF:

0.596

Gnomad NFE

AF:

0.674

Gnomad OTH

AF:

0.551

GnomAD3 exomes

AF:

0.534

AC:

134214

AN:

251384

Hom.:

40055

AF XY:

0.546

AC XY:

74132

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.257

Gnomad AMR exome

AF:

0.373

Gnomad ASJ exome

AF:

0.700

Gnomad EAS exome

AF:

0.165

Gnomad SAS exome

AF:

0.428

Gnomad FIN exome

AF:

0.625

Gnomad NFE exome

AF:

0.675

Gnomad OTH exome

AF:

0.604

GnomAD4 exome

AF:

0.622

AC:

905897

AN:

1455388

Hom.:

294692

Cov.:

AF XY:

0.620

AC XY:

449067

AN XY:

724342

show subpopulations

Gnomad4 AFR exome

AF:

0.251

Gnomad4 AMR exome

AF:

0.388

Gnomad4 ASJ exome

AF:

0.699

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.426

Gnomad4 FIN exome

AF:

0.633

Gnomad4 NFE exome

AF:

0.675

Gnomad4 OTH exome

AF:

0.598

GnomAD4 genome

AF:

0.514

AC:

78061

AN:

151860

Hom.:

22805

Cov.:

AF XY:

0.506

AC XY:

37533

AN XY:

74238

show subpopulations

Gnomad4 AFR

AF:

0.268

Gnomad4 AMR

AF:

0.484

Gnomad4 ASJ

AF:

0.704

Gnomad4 EAS

AF:

0.162

Gnomad4 SAS

AF:

0.410

Gnomad4 FIN

AF:

0.627

Gnomad4 NFE

AF:

0.674

Gnomad4 OTH

AF:

0.546

Alfa

AF:

0.650

Hom.:

55381

Bravo

AF:

0.493

Asia WGS

AF:

0.285

AC:

991

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

-0.90

CADD

Benign

0.057

DANN

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over