rs11034170

chr11-4841623-C-T

Variant summary

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

The NM_021801.5(MMP26):c.-145+74282C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,996 control chromosomes in the GnomAD database, including 11,059 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 0.37 (11059 hom., cov: 32)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.145

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP26	NM_021801.5	c.-145+74282C>T		intron_variant		ENST00000380390.6
MMP26	NM_001384608.1	c.-153+74282C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP26	ENST00000380390.6	c.-145+74282C>T		intron_variant		5	NM_021801.5	P1
MMP26	ENST00000300762.2	c.-153+74282C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56466 AN: 151880 Hom.: 11062 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.372 AC: 56474 AN: 151996 Hom.: 11059 Cov.: 32 AF XY: 0.368 AC XY: 27322 AN XY: 74304

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.0868

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.387

Alfa AF: 0.414 Hom.: 16885

Bravo AF: 0.365

Asia WGS AF: 0.323 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.7
Dann	Benign	0.78

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: rs11034170; hg19: chr11-4862853;