20-45305320-C-T

Position:

• chr20-45305320-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393530.1(MATN4):​c.73+190G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 152,182 control chromosomes in the GnomAD database, including 6,172 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 0.25 (6172 hom., cov: 33)
• Consequence: MATN4 NM_001393530.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

Genes affected

MATN4 (HGNC:6910): (matrilin 4) This gene encodes a member of von Willebrand factor A domain-containing protein family. The proteins of this family are thought to be involved in the formation of filamentous networks in the extracellular matrices of various tissues. This family member is thought to be play a role in reorganizing and regenerating the corneal matrix in granular and lattice type I dystrophies. It may also be involved in wound healing in the dentin-pulp complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MATN4	NM_001393530.1	c.73+190G>A		intron_variant		ENST00000372756.6	NP_001380459.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MATN4	ENST00000372756.6	c.73+190G>A		intron_variant		1	NM_001393530.1	ENSP00000361842

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38199 AN: 152064 Hom.: 6170 Cov.: 33

Gnomad AFR AF: 0.102

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.743

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.275

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.251 AC: 38208 AN: 152182 Hom.: 6172 Cov.: 33 AF XY: 0.257 AC XY: 19150 AN XY: 74398

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.259

Alfa AF: 0.245 Hom.: 1606

Bravo AF: 0.252

Asia WGS AF: 0.552 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.9
DANN	Benign	0.51

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: rs2072787; hg19: chr20-43933960;