rs1433897

Positions:

• chr11-4920674-A-G
• chr11-4920674-A-T

Variant summary

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

The NM_021801.5(MMP26):​c.-144-67394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,998 control chromosomes in the GnomAD database, including 28,774 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 0.61 (28774 hom., cov: 32)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP26	NM_021801.5	c.-144-67394A>G		intron_variant		ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-152-67596A>G		intron_variant			NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP26	ENST00000380390.6	c.-144-67394A>G		intron_variant		5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-152-67596A>G		intron_variant		1		ENSP00000300762.2

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92954 AN: 151878 Hom.: 28737 Cov.: 32

Gnomad AFR AF: 0.686

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.686

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.580

Gnomad OTH AF: 0.602

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

GnomAD4 genome AF: 0.612 AC: 93056 AN: 151998 Hom.: 28774 Cov.: 32 AF XY: 0.609 AC XY: 45255 AN XY: 74274

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.685

Gnomad4 SAS AF: 0.581

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.580

Gnomad4 OTH AF: 0.605

Alfa AF: 0.579 Hom.: 49265

Bravo AF: 0.632

Asia WGS AF: 0.653 AC: 2269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.0
DANN	Benign	0.82

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: rs1433897; hg19: chr11-4941904;