14-22841276-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004995.4(MMP14):c.109-215C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 152,174 control chromosomes in the GnomAD database, including 7,074 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (7074 hom., cov: 34)
• Consequence: MMP14 NM_004995.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.711

Genes affected

MMP14 (HGNC:7160): (matrix metallopeptidase 14) 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. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are expressed at the cell surface rather than secreted. This protein activates MMP2 protein, and this activity may be involved in tumor invasion. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 14-22841276-C-T is Benign according to our data. Variant chr14-22841276-C-T is described in ClinVar as [Benign]. Clinvar id is 1286498.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP14	NM_004995.4	c.109-215C>T		intron_variant		ENST00000311852.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP14	ENST00000311852.11	c.109-215C>T		intron_variant		1	NM_004995.4	P1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 44001 AN: 152056 Hom.: 7074 Cov.: 34

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.376

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.284

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

GnomAD4 genome AF: 0.289 AC: 44014 AN: 152174 Hom.: 7074 Cov.: 34 AF XY: 0.294 AC XY: 21886 AN XY: 74390

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.376

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.282

Alfa AF: 0.323 Hom.: 13532

Bravo AF: 0.285

Asia WGS AF: 0.331 AC: 1151 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	8.0
Dann	Benign	0.73

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: rs8006914; hg19: chr14-23310485;