rs2236304

Variant names:

• chr14-22843654-C-G
• rs2236304
• NM_004995.4:c.851-56C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-22843654-C-G
• chr14-22843654-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004995.4(MMP14):​c.851-56C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,541,604 control chromosomes in the GnomAD database, including 81,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6931 hom., cov: 31)
  • Exomes 𝑓: 0.32 (74341 hom.)
• Consequence: MMP14 NM_004995.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.278
• Publications: 11 publications found

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 Gene-Disease associations (from GenCC):

• Winchester syndrome

  Inheritance: AR, Unknown Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• multicentric osteolysis-nodulosis-arthropathy spectrum

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 14-22843654-C-G is Benign according to our data. Variant chr14-22843654-C-G is described in ClinVar as Benign. ClinVar VariationId is 1272389.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004995.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP14	NM_004995.4	MANE Select	c.851-56C>G		intron	N/A	NP_004986.1	P50281

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP14	ENST00000311852.11	TSL:1 MANE Select	c.851-56C>G		intron	N/A	ENSP00000308208.6	P50281
	MMP14	ENST00000928197.1		c.665-56C>G		intron	N/A	ENSP00000598256.1
	MMP14	ENST00000548162.2	TSL:5	c.851-56C>G		intron	N/A	ENSP00000506068.1	A0A7P0TAG0

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42813 AN: 151826 Hom.: 6929 Cov.: 31

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.467

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.322 AC: 447690 AN: 1389660 Hom.: 74341 Cov.: 28 AF XY: 0.320 AC XY: 219643 AN XY: 686788

African (AFR) AF: 0.114 AC: 3494 AN: 30684

American (AMR) AF: 0.465 AC: 15324 AN: 32982

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 8483 AN: 22142

East Asian (EAS) AF: 0.474 AC: 18432 AN: 38926

South Asian (SAS) AF: 0.251 AC: 19174 AN: 76466

European-Finnish (FIN) AF: 0.383 AC: 19716 AN: 51532

Middle Eastern (MID) AF: 0.317 AC: 1719 AN: 5430

European-Non Finnish (NFE) AF: 0.319 AC: 343015 AN: 1074152

Other (OTH) AF: 0.320 AC: 18333 AN: 57346

GnomAD4 genome AF: 0.282 AC: 42819 AN: 151944 Hom.: 6931 Cov.: 31 AF XY: 0.287 AC XY: 21326 AN XY: 74228

African (AFR) AF: 0.122 AC: 5069 AN: 41462

American (AMR) AF: 0.377 AC: 5757 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3468

East Asian (EAS) AF: 0.467 AC: 2393 AN: 5124

South Asian (SAS) AF: 0.259 AC: 1246 AN: 4814

European-Finnish (FIN) AF: 0.393 AC: 4145 AN: 10538

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22130 AN: 67960

Other (OTH) AF: 0.281 AC: 591 AN: 2106

Alfa AF: 0.299 Hom.: 901

Bravo AF: 0.278

Asia WGS AF: 0.338 AC: 1175 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.9
DANN	Benign	0.65
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2236304; hg19: chr14-23312863; COSMIC: COSV61287316; COSMIC: COSV61287316;