rs11034170

Variant names:

• chr11-4841623-C-T
• rs11034170
• NM_021801.5:c.-145+74282C>T

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.87).
• 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 rank	MANE	Protein	UniProt
MMP26	NM_021801.5	c.-145+74282C>T		intron_variant	Intron 2 of 7	ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-153+74282C>T		intron_variant	Intron 2 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP26	ENST00000380390.6	c.-145+74282C>T		intron_variant	Intron 2 of 7	5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-153+74282C>T		intron_variant	Intron 2 of 7	1		ENSP00000300762.2

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

African (AFR) AF: 0.348 AC: 14417 AN: 41424

American (AMR) AF: 0.299 AC: 4570 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1712 AN: 3466

East Asian (EAS) AF: 0.0868 AC: 449 AN: 5170

South Asian (SAS) AF: 0.551 AC: 2654 AN: 4818

European-Finnish (FIN) AF: 0.321 AC: 3389 AN: 10554

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27878 AN: 67966

Other (OTH) AF: 0.387 AC: 816 AN: 2110

Alfa AF: 0.409 Hom.: 21627

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
PhyloP100		0.14
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: rs11034170; hg19: chr11-4862853;