20-45305320-C-T

Variant names:

• chr20-45305320-C-T
• rs2072787
• NM_001393530.1:c.73+190G>A

Variant summary

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

The NM_003833.5(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_003833.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003833.5. 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
	MATN4	NM_001393530.1	MANE Select	c.73+190G>A		intron	N/A	NP_001380459.1
	MATN4	NM_003833.5		c.73+190G>A		intron	N/A	NP_003824.2
	MATN4	NM_001393531.1		c.73+190G>A		intron	N/A	NP_001380460.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MATN4	ENST00000372756.6	TSL:1 MANE Select	c.73+190G>A		intron	N/A	ENSP00000361842.1
	MATN4	ENST00000372754.5	TSL:5	c.73+190G>A		intron	N/A	ENSP00000361840.1
	MATN4	ENST00000360607.10	TSL:1	c.73+190G>A		intron	N/A	ENSP00000353819.5

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

African (AFR) AF: 0.102 AC: 4229 AN: 41538

American (AMR) AF: 0.314 AC: 4801 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3466

East Asian (EAS) AF: 0.744 AC: 3854 AN: 5180

South Asian (SAS) AF: 0.422 AC: 2035 AN: 4822

European-Finnish (FIN) AF: 0.253 AC: 2673 AN: 10584

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.275 AC: 18666 AN: 67982

Other (OTH) AF: 0.259 AC: 546 AN: 2110

Alfa AF: 0.245 Hom.: 2008

Bravo AF: 0.252

Asia WGS AF: 0.552 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.9
DANN	Benign	0.51
PhyloP100		1.1
PromoterAI		0.012	Neutral
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: rs2072787; hg19: chr20-43933960;