rs11034990

Variant names:

• chr11-4984455-T-C
• rs11034990
• NM_021801.5:c.-144-3613T>C

Variant summary

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

The NM_021801.5(MMP26):​c.-144-3613T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,234 control chromosomes in the GnomAD database, including 1,819 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 0.13 (1819 hom., cov: 32)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.389
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021801.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP26	NM_021801.5	MANE Select	c.-144-3613T>C		intron	N/A	NP_068573.2
	MMP26	NM_001384608.1		c.-152-3815T>C		intron	N/A	NP_001371537.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP26	ENST00000380390.6	TSL:5 MANE Select	c.-144-3613T>C		intron	N/A	ENSP00000369753.1
	MMP26	ENST00000300762.2	TSL:1	c.-152-3815T>C		intron	N/A	ENSP00000300762.2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20407 AN: 152116 Hom.: 1817 Cov.: 32

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.0774

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.126

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

GnomAD4 genome AF: 0.134 AC: 20404 AN: 152234 Hom.: 1819 Cov.: 32 AF XY: 0.137 AC XY: 10168 AN XY: 74422

African (AFR) AF: 0.0318 AC: 1322 AN: 41580

American (AMR) AF: 0.229 AC: 3497 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 482 AN: 3468

East Asian (EAS) AF: 0.0766 AC: 397 AN: 5184

South Asian (SAS) AF: 0.101 AC: 488 AN: 4824

European-Finnish (FIN) AF: 0.206 AC: 2186 AN: 10596

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11580 AN: 67984

Other (OTH) AF: 0.124 AC: 262 AN: 2108

Alfa AF: 0.158 Hom.: 4771

Bravo AF: 0.131

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.28
PhyloP100		0.39
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: rs11034990; hg19: chr11-5005685;