NM_198129.4:c.1603+1732A>G

Variant names:

• chr18-23785889-A-G
• rs11082762
• NM_198129.4:c.1603+1732A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198129.4(LAMA3):​c.1603+1732A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 152,074 control chromosomes in the GnomAD database, including 19,382 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 0.48 (19382 hom., cov: 32)
• Consequence: LAMA3 NM_198129.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• junctional epidermolysis bullosa

  Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health
• laryngo-onycho-cutaneous syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
• junctional epidermolysis bullosa Herlitz type

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
• junctional epidermolysis bullosa, non-Herlitz type

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Genomics England PanelApp
• generalized junctional epidermolysis bullosa non-Herlitz type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198129.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA3	NM_198129.4	MANE Select	c.1603+1732A>G		intron	N/A	NP_937762.2
	LAMA3	NM_001127717.4		c.1603+1732A>G		intron	N/A	NP_001121189.2
	LAMA3	NR_130106.2		n.1834+1732A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LAMA3	ENST00000313654.14	TSL:1 MANE Select	c.1603+1732A>G		intron	N/A	ENSP00000324532.8
	LAMA3	ENST00000399516.7	TSL:1	c.1603+1732A>G		intron	N/A	ENSP00000382432.2
	LAMA3	ENST00000585600.5	TSL:1	n.1603+1732A>G		intron	N/A	ENSP00000468316.1

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73174 AN: 151956 Hom.: 19378 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.554

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.515

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.481 AC: 73193 AN: 152074 Hom.: 19382 Cov.: 32 AF XY: 0.473 AC XY: 35136 AN XY: 74324

African (AFR) AF: 0.299 AC: 12398 AN: 41474

American (AMR) AF: 0.450 AC: 6887 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2285 AN: 3468

East Asian (EAS) AF: 0.170 AC: 882 AN: 5180

South Asian (SAS) AF: 0.361 AC: 1738 AN: 4816

European-Finnish (FIN) AF: 0.554 AC: 5845 AN: 10556

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.607 AC: 41289 AN: 67966

Other (OTH) AF: 0.512 AC: 1081 AN: 2112

Alfa AF: 0.510 Hom.: 19953

Bravo AF: 0.469

Asia WGS AF: 0.264 AC: 921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.55
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11082762; hg19: chr18-21365853;