11-102716423-G-T

Variant names:

• chr11-102716423-G-T
• rs1458854194
• NM_002424.3:c.785-4C>A

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002424.3. 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
	MMP8	NM_002424.3	MANE Select	c.785-4C>A		splice_region intron	N/A	NP_002415.1	P22894
	MMP8	NM_001304441.2		c.716-4C>A		splice_region intron	N/A	NP_001291370.1
	MMP8	NM_001304442.2		c.716-4C>A		splice_region intron	N/A	NP_001291371.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MMP8	ENST00000236826.8	TSL:1 MANE Select	c.785-4C>A		splice_region intron	N/A	ENSP00000236826.3	P22894
	MMP8	ENST00000438475.2	TSL:5	c.710-4C>A		splice_region intron	N/A	ENSP00000401004.2	H7C1M3
	MMP8	ENST00000528662.6	TSL:5	n.*762-4C>A		splice_region intron	N/A	ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes AF: 0.0000228 AC: 2 AN: 87676 Hom.: 0 Cov.: 12

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000496 AC: 3 AN: 6048

American (AMR) AF: 0.00 AC: 0 AN: 13538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6336

East Asian (EAS) AF: 0.000125 AC: 2 AN: 16022

South Asian (SAS) AF: 0.00 AC: 0 AN: 32364

European-Finnish (FIN) AF: 0.0000453 AC: 1 AN: 22074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1086

European-Non Finnish (NFE) AF: 0.000285 AC: 56 AN: 196836

Other (OTH) AF: 0.000292 AC: 4 AN: 13682

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21016

American (AMR) AF: 0.00 AC: 0 AN: 7626

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2484

East Asian (EAS) AF: 0.00 AC: 0 AN: 2892

South Asian (SAS) AF: 0.00 AC: 0 AN: 2174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 152

European-Non Finnish (NFE) AF: 0.0000422 AC: 2 AN: 47410

Other (OTH) AF: 0.00 AC: 0 AN: 1182

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000203476), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.21
DANN	Benign	0.25
PhyloP100		-0.52

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

Other links and lift over

dbSNP: rs1458854194; hg19: chr11-102587154;