11-102716423-G-T

Variant names:

• chr11-102716423-G-T
• NM_002424.3:c.785-4C>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002424.3(MMP8):​c.785-4C>A variant causes a splice region, 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000023 (0 hom., cov: 12)
  • Exomes 𝑓: 0.00021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MMP8 NM_002424.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002312
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP8	NM_002424.3	c.785-4C>A		splice_region_variant, intron_variant	Intron 5 of 9	ENST00000236826.8	NP_002415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP8	ENST00000236826.8	c.785-4C>A		splice_region_variant, intron_variant	Intron 5 of 9	1	NM_002424.3	ENSP00000236826.3
MMP8	ENST00000438475.2	c.710-4C>A		splice_region_variant, intron_variant	Intron 5 of 8	5		ENSP00000401004.2
MMP8	ENST00000528662.6	n.*762-4C>A		splice_region_variant, intron_variant	Intron 7 of 11	5		ENSP00000431431.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 2 AN: 87676 Hom.: 0 Cov.: 12 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000422

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000214 AC: 66 AN: 307986 Hom.: 0 Cov.: 7 AF XY: 0.000214 AC XY: 36 AN XY: 168178

Gnomad4 AFR exome AF: 0.000496

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000125

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000453

Gnomad4 NFE exome AF: 0.000285

Gnomad4 OTH exome AF: 0.000292

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000228 AC: 2 AN: 87656 Hom.: 0 Cov.: 12 AF XY: 0.0000503 AC XY: 2 AN XY: 39772

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000422

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-102587154;