rs12786973

Positions:

• chr11-4834217-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+66876C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0966 in 152,162 control chromosomes in the GnomAD database, including 849 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 0.097 (849 hom., cov: 32)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.407

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=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP26	NM_021801.5	c.-145+66876C>T		intron_variant		ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-153+66876C>T		intron_variant			NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP26	ENST00000380390.6	c.-145+66876C>T		intron_variant		5	NM_021801.5	ENSP00000369753	P1
MMP26	ENST00000300762.2	c.-153+66876C>T		intron_variant		1		ENSP00000300762

Frequencies

GnomAD3 genomes AF: 0.0966 AC: 14695 AN: 152044 Hom.: 850 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0269

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.126

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.0966 AC: 14692 AN: 152162 Hom.: 849 Cov.: 32 AF XY: 0.0936 AC XY: 6959 AN XY: 74374

Gnomad4 AFR AF: 0.0517

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0272

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.126

Gnomad4 OTH AF: 0.116

Alfa AF: 0.101 Hom.: 100

Bravo AF: 0.0962

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	13
DANN	Benign	0.84

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: rs12786973; hg19: chr11-4855447;