18-23690207-A-C

Position:

• chr18-23690207-A-C

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+230A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,046 control chromosomes in the GnomAD database, including 25,447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.57 (25447 hom., cov: 32)
• Consequence: LAMA3 NM_198129.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.03

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=-0.85).
• BP6: Variant 18-23690207-A-C is Benign according to our data. Variant chr18-23690207-A-C is described in ClinVar as [Benign]. Clinvar id is 1261977.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LAMA3	NM_198129.4	c.294+230A>C		intron_variant		ENST00000313654.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LAMA3	ENST00000313654.14	c.294+230A>C		intron_variant		1	NM_198129.4	P1
LAMA3	ENST00000399516.7	c.294+230A>C		intron_variant		1
LAMA3	ENST00000585600.5	c.294+230A>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87140 AN: 151928 Hom.: 25419 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.568

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.589

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

GnomAD4 genome AF: 0.574 AC: 87219 AN: 152046 Hom.: 25447 Cov.: 32 AF XY: 0.571 AC XY: 42426 AN XY: 74320

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.639

Gnomad4 ASJ AF: 0.659

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.568

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.587

Alfa AF: 0.597 Hom.: 3396

Bravo AF: 0.577

Asia WGS AF: 0.404 AC: 1406 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

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.025
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2960586; hg19: chr18-21270171; COSMIC: COSV58081471;