11-102716423-G-A

Position:

• chr11-102716423-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_002424.3(MMP8):​c.785-4C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 12)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: MMP8 NM_002424.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002312
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.515

Genes affected

MMP8 (HGNC:7175): (matrix metallopeptidase 8) This gene encodes a member of the matrix metalloproteinase (MMP) family of proteins. These proteins are involved in the breakdown of extracellular matrix in embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Proteolysis at different sites on this protein results in multiple active forms of the enzyme with distinct N-termini. This protein functions in the degradation of type I, II and III collagens. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 11-102716423-G-A is Benign according to our data. Variant chr11-102716423-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 724355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP8	NM_002424.3	c.785-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8	c.785-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_002424.3	ENSP00000236826	P1
MMP8	ENST00000438475.2	c.711-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		5		ENSP00000401004
MMP8	ENST00000528662.6	c.*762-4C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5		ENSP00000431431

Frequencies

GnomAD3 genomes AF: 0.000183 AC: 16 AN: 87666 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.0000952

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000491

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000148

Gnomad OTH AF: 0.00169

GnomAD4 exome AF: 0.00148 AC: 455 AN: 307606 Hom.: 0 Cov.: 7 AF XY: 0.00151 AC XY: 253 AN XY: 167934

Gnomad4 AFR exome AF: 0.00116

Gnomad4 AMR exome AF: 0.00118

Gnomad4 ASJ exome AF: 0.00174

Gnomad4 EAS exome AF: 0.00156

Gnomad4 SAS exome AF: 0.00223

Gnomad4 FIN exome AF: 0.000544

Gnomad4 NFE exome AF: 0.00148

Gnomad4 OTH exome AF: 0.00154

GnomAD4 genome AF: 0.000183 AC: 16 AN: 87646 Hom.: 0 Cov.: 12 AF XY: 0.000201 AC XY: 8 AN XY: 39766

Gnomad4 AFR AF: 0.0000952

Gnomad4 AMR AF: 0.000525

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000491

Gnomad4 NFE AF: 0.000148

Gnomad4 OTH AF: 0.00169

Alfa AF: 0.000843 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 17, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.27
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0
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: rs1458854194; hg19: chr11-102587154; COSMIC: COSV52634181;