rs1458854194

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr11-102716423-G-A
• chr11-102716423-G-C
• chr11-102716423-G-T

Variant summary

Our verdict is Benign. The variant received -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, 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, intron
• Scores: Splicing: ADA: 0.00002312
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -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 VariationId is 724355.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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>T		splice_region intron	N/A	NP_002415.1	P22894
	MMP8	NM_001304441.2		c.716-4C>T		splice_region intron	N/A	NP_001291370.1
	MMP8	NM_001304442.2		c.716-4C>T		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>T		splice_region intron	N/A	ENSP00000236826.3	P22894
	MMP8	ENST00000438475.2	TSL:5	c.710-4C>T		splice_region intron	N/A	ENSP00000401004.2	H7C1M3
	MMP8	ENST00000528662.6	TSL:5	n.*762-4C>T		splice_region intron	N/A	ENSP00000431431.2	E9PL87

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

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

African (AFR) AF: 0.00116 AC: 7 AN: 6040

American (AMR) AF: 0.00118 AC: 16 AN: 13530

Ashkenazi Jewish (ASJ) AF: 0.00174 AC: 11 AN: 6330

East Asian (EAS) AF: 0.00156 AC: 25 AN: 16014

South Asian (SAS) AF: 0.00223 AC: 72 AN: 32284

European-Finnish (FIN) AF: 0.000544 AC: 12 AN: 22042

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

European-Non Finnish (NFE) AF: 0.00148 AC: 291 AN: 196612

Other (OTH) AF: 0.00154 AC: 21 AN: 13668

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

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

African (AFR) AF: 0.0000952 AC: 2 AN: 21014

American (AMR) AF: 0.000525 AC: 4 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: 0.000491 AC: 1 AN: 2036

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

European-Non Finnish (NFE) AF: 0.000148 AC: 7 AN: 47402

Other (OTH) AF: 0.00169 AC: 2 AN: 1182

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.000843 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely 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	-0.94
CADD	Benign	0.27
DANN	Benign	0.28
PhyloP100		-0.52
Mutation Taster		=100/0	polymorphism

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; COSMIC: COSV52634181;