11-4755697-A-G

Position:

• chr11-4755697-A-G

Variant summary

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

The NM_021801.5(MMP26):​c.-216-11573A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 152,060 control chromosomes in the GnomAD database, including 640 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 0.067 (640 hom., cov: 32)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP26	NM_021801.5	c.-216-11573A>G		intron_variant		ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-224-11573A>G		intron_variant			NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP26	ENST00000380390.6	c.-216-11573A>G		intron_variant		5	NM_021801.5	ENSP00000369753	P1
MMP26	ENST00000300762.2	c.-224-11573A>G		intron_variant		1		ENSP00000300762

Frequencies

GnomAD3 genomes AF: 0.0673 AC: 10220 AN: 151942 Hom.: 639 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0367

Gnomad ASJ AF: 0.0972

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.0894

Gnomad FIN AF: 0.0311

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0590

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

GnomAD4 genome AF: 0.0673 AC: 10241 AN: 152060 Hom.: 640 Cov.: 32 AF XY: 0.0673 AC XY: 5001 AN XY: 74348

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0972

Gnomad4 EAS AF: 0.0590

Gnomad4 SAS AF: 0.0884

Gnomad4 FIN AF: 0.0311

Gnomad4 NFE AF: 0.0189

Gnomad4 OTH AF: 0.0598

Alfa AF: 0.0530 Hom.: 57

Bravo AF: 0.0762

Asia WGS AF: 0.0990 AC: 345 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7940199; hg19: chr11-4776927;