rs12271916

Variant names:

• chr11-4705648-G-A
• rs12271916
• NM_021801.5:c.-217+603G>A

Variant summary

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

The NM_021801.5(MMP26):​c.-217+603G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,100 control chromosomes in the GnomAD database, including 3,823 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 0.16 (3823 hom., cov: 31)
• Consequence: MMP26 NM_021801.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.523
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP26	NM_021801.5	c.-217+603G>A		intron_variant	Intron 1 of 7	ENST00000380390.6	NP_068573.2
MMP26	NM_001384608.1	c.-225+603G>A		intron_variant	Intron 1 of 7		NP_001371537.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP26	ENST00000380390.6	c.-217+603G>A		intron_variant	Intron 1 of 7	5	NM_021801.5	ENSP00000369753.1
MMP26	ENST00000300762.2	c.-225+603G>A		intron_variant	Intron 1 of 7	1		ENSP00000300762.2

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24417 AN: 151982 Hom.: 3816 Cov.: 31

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.0760

Gnomad FIN AF: 0.0320

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0485

Gnomad OTH AF: 0.156

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

GnomAD4 genome AF: 0.161 AC: 24458 AN: 152100 Hom.: 3823 Cov.: 31 AF XY: 0.159 AC XY: 11797 AN XY: 74368

African (AFR) AF: 0.398 AC: 16504 AN: 41440

American (AMR) AF: 0.107 AC: 1635 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 515 AN: 3468

East Asian (EAS) AF: 0.270 AC: 1396 AN: 5168

South Asian (SAS) AF: 0.0746 AC: 360 AN: 4826

European-Finnish (FIN) AF: 0.0320 AC: 339 AN: 10596

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.0485 AC: 3296 AN: 67996

Other (OTH) AF: 0.158 AC: 334 AN: 2112

Alfa AF: 0.120 Hom.: 3583

Bravo AF: 0.179

Asia WGS AF: 0.187 AC: 651 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.6
DANN	Benign	0.65
PhyloP100		0.52

Splicing

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

Other links and lift over

dbSNP: rs12271916; hg19: chr11-4726878;