rs1555322

Positions:

• chr20-35261376-G-A

Variant summary

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

The NM_006690.4(MMP24):​c.818-2415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,172 control chromosomes in the GnomAD database, including 1,498 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 0.14 (1498 hom., cov: 32)
• Consequence: MMP24 NM_006690.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.811

Genes affected

MMP24 (HGNC:7172): (matrix metallopeptidase 24) This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. Unlike most MMPs, which are secreted, this protease is a member of the membrane-type MMP (MT-MMP) subfamily, contains a transmembrane domain and is expressed at the cell surface. Substrates of this protease include the proteins cadherin 2 and matrix metallopeptidase 2 (also known as 72 kDa type IV collagenase). The gene has previously been referred to as MMP25 but has been renamed matrix metallopeptidase 24 (MMP24). [provided by RefSeq, Oct 2019]

MMP24-AS1-EDEM2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP24	NM_006690.4	c.818-2415G>A		intron_variant		ENST00000246186.8	NP_006681.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP24	ENST00000246186.8	c.818-2415G>A		intron_variant		1	NM_006690.4	ENSP00000246186.6

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20758 AN: 152054 Hom.: 1496 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.136 AC: 20765 AN: 152172 Hom.: 1498 Cov.: 32 AF XY: 0.134 AC XY: 9977 AN XY: 74398

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.125

Alfa AF: 0.130 Hom.: 2171

Bravo AF: 0.134

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.095
DANN	Benign	0.69

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: rs1555322; hg19: chr20-33849179;