Variant rs2236303 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_004995.4(MMP14):c.850+91C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,491,366 control chromosomes in the GnomAD database, including 75,849 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.27 ( 6518 hom., cov: 31)

Exomes 𝑓: 0.32 ( 69331 hom. )

Consequence

MMP14
NM_004995.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.270

Variant links:

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]

MMP14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 14-22843509-C-T is Benign according to our data. Variant chr14-22843509-C-T is described in ClinVar as [Benign]. Clinvar id is 1271157.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP14	NM_004995.4 linkuse as main transcript	c.850+91C>T		intron_variant		ENST00000311852.11

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
MMP14	ENST00000311852.11 linkuse as main transcript	c.850+91C>T	intron_variant	1	NM_004995.4	P1
MMP14	ENST00000548162.2 linkuse as main transcript	c.850+91C>T	intron_variant	5
MMP14	ENST00000680097.1 linkuse as main transcript	c.*165+91C>T	intron_variant, NMD_transcript_variant
MMP14	ENST00000680941.1 linkuse as main transcript	c.*248+91C>T	intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

40673

AN:

151760

Hom.:

6515

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0909

Gnomad AMI

AF:

0.147

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.479

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.369

Gnomad MID

AF:

0.263

Gnomad NFE

AF:

0.318

Gnomad OTH

AF:

0.274

GnomAD4 exome

AF:

0.316

AC:

423005

AN:

1339488

Hom.:

69331

Cov.:

AF XY:

0.314

AC XY:

207285

AN XY:

660596

show subpopulations

Gnomad4 AFR exome

AF:

0.0821

Gnomad4 AMR exome

AF:

0.480

Gnomad4 ASJ exome

AF:

0.379

Gnomad4 EAS exome

AF:

0.484

Gnomad4 SAS exome

AF:

0.251

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.312

Gnomad4 OTH exome

AF:

0.313

GnomAD4 genome

AF:

0.268

AC:

40681

AN:

151878

Hom.:

6518

Cov.:

AF XY:

0.273

AC XY:

20268

AN XY:

74202

show subpopulations

Gnomad4 AFR

AF:

0.0908

Gnomad4 AMR

AF:

0.372

Gnomad4 ASJ

AF:

0.362

Gnomad4 EAS

AF:

0.479

Gnomad4 SAS

AF:

0.257

Gnomad4 FIN

AF:

0.369

Gnomad4 NFE

AF:

0.318

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.296

Hom.:

1708

Bravo

AF:

0.265

Asia WGS

AF:

0.336

AC:

1167

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over