rs4432013

Positions:

• chr11-4709950-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_021801.5(MMP26):​c.-217+4905G>A variant causes a intron change. The variant allele was found at a frequency of 0.827 in 456,824 control chromosomes in the GnomAD database, including 157,217 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 0.83 (53239 hom., cov: 32)
  • Exomes 𝑓: 0.82 (103978 hom.)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.34

Genes affected

MMP26 (HGNC:14249): (matrix metallopeptidase 26) Proteins of the matrix metalloproteinase (MMP) 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 enzyme. This enzyme may degrade collagen type IV, fibronectin, fibrinogen, and beta-casein, and activate matrix metalloproteinase-9 by cleavage. The protein differs from most MMP family members in that it lacks a conserved C-terminal protein domain. The encoded protein may promote cell invasion in multiple human cancers. [provided by RefSeq, May 2016]

OR51F5P (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.891 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP26	NM_021801.5	c.-217+4905G>A		intron_variant		ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-225+4905G>A		intron_variant			NP_001371537.1
OR51F5P		n.4709950G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP26	ENST00000380390.6	c.-217+4905G>A		intron_variant		5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-225+4905G>A		intron_variant		1		ENSP00000300762.2
OR51F5P	ENST00000609912.1	n.382G>A		non_coding_transcript_exon_variant	1/1	6
ENSG00000290647	ENST00000641454.1	n.382G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.834 AC: 126893 AN: 152084 Hom.: 53212 Cov.: 32

Gnomad AFR AF: 0.900

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.814

Gnomad ASJ AF: 0.771

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.892

Gnomad FIN AF: 0.925

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.792

Gnomad OTH AF: 0.794

GnomAD3 exomes AF: 0.823 AC: 113252 AN: 137666 Hom.: 46906 AF XY: 0.824 AC XY: 61527 AN XY: 74678

Gnomad AFR exome AF: 0.906

Gnomad AMR exome AF: 0.847

Gnomad ASJ exome AF: 0.767

Gnomad EAS exome AF: 0.737

Gnomad SAS exome AF: 0.893

Gnomad FIN exome AF: 0.911

Gnomad NFE exome AF: 0.789

Gnomad OTH exome AF: 0.793

GnomAD4 exome AF: 0.824 AC: 251048 AN: 304622 Hom.: 103978 Cov.: 0 AF XY: 0.828 AC XY: 143663 AN XY: 173454

Gnomad4 AFR exome AF: 0.902

Gnomad4 AMR exome AF: 0.846

Gnomad4 ASJ exome AF: 0.772

Gnomad4 EAS exome AF: 0.747

Gnomad4 SAS exome AF: 0.890

Gnomad4 FIN exome AF: 0.904

Gnomad4 NFE exome AF: 0.796

Gnomad4 OTH exome AF: 0.800

GnomAD4 genome AF: 0.834 AC: 126970 AN: 152202 Hom.: 53239 Cov.: 32 AF XY: 0.841 AC XY: 62565 AN XY: 74424

Gnomad4 AFR AF: 0.899

Gnomad4 AMR AF: 0.814

Gnomad4 ASJ AF: 0.771

Gnomad4 EAS AF: 0.758

Gnomad4 SAS AF: 0.891

Gnomad4 FIN AF: 0.925

Gnomad4 NFE AF: 0.792

Gnomad4 OTH AF: 0.792

Alfa AF: 0.815 Hom.: 14436

Bravo AF: 0.826

Asia WGS AF: 0.833 AC: 2898 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	18
DANN	Benign	0.85

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4432013; hg19: chr11-4731180;