11-102715443-G-A

Variant names:

• chr11-102715443-G-A
• rs34799325
• NM_002424.3:c.903-6C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002424.3(MMP8):​c.903-6C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000761 in 1,608,552 control chromosomes in the GnomAD database, including 9 homozygotes. 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 Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 31)
  • Exomes 𝑓: 0.00059 (7 hom.)
• Consequence: MMP8 NM_002424.3 splice_region, intron
• Scores: Splicing: ADA: 0.00002130
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.750
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 11-102715443-G-A is Benign according to our data. Variant chr11-102715443-G-A is described in ClinVar as Benign. ClinVar VariationId is 708208.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 gene

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.903-6C>T		splice_region intron	N/A	NP_002415.1	P22894
	MMP8	NM_001304441.2		c.834-6C>T		splice_region intron	N/A	NP_001291370.1
	MMP8	NM_001304442.2		c.834-6C>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.903-6C>T		splice_region intron	N/A	ENSP00000236826.3	P22894
	MMP8	ENST00000438475.2	TSL:5	c.828-6C>T		splice_region intron	N/A	ENSP00000401004.2	H7C1M3
	MMP8	ENST00000528662.6	TSL:5	n.*880-6C>T		splice_region intron	N/A	ENSP00000431431.2	E9PL87

Frequencies

GnomAD3 genomes AF: 0.00245 AC: 372 AN: 152058 Hom.: 2 Cov.: 31

Gnomad AFR AF: 0.00751

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000853

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000515

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.000971 AC: 237 AN: 244142 AF XY: 0.000788

Gnomad AFR exome AF: 0.00818

Gnomad AMR exome AF: 0.000479

Gnomad ASJ exome AF: 0.00178

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000470

Gnomad OTH exome AF: 0.000838

GnomAD4 exome AF: 0.000585 AC: 852 AN: 1456376 Hom.: 7 Cov.: 31 AF XY: 0.000559 AC XY: 405 AN XY: 724448

African (AFR) AF: 0.00803 AC: 266 AN: 33124

American (AMR) AF: 0.000639 AC: 28 AN: 43830

Ashkenazi Jewish (ASJ) AF: 0.00171 AC: 44 AN: 25756

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39644

South Asian (SAS) AF: 0.000480 AC: 41 AN: 85404

European-Finnish (FIN) AF: 0.0000189 AC: 1 AN: 53020

Middle Eastern (MID) AF: 0.000524 AC: 3 AN: 5720

European-Non Finnish (NFE) AF: 0.000388 AC: 431 AN: 1109722

Other (OTH) AF: 0.000615 AC: 37 AN: 60156

GnomAD4 genome AF: 0.00244 AC: 372 AN: 152176 Hom.: 2 Cov.: 31 AF XY: 0.00247 AC XY: 184 AN XY: 74400

African (AFR) AF: 0.00749 AC: 311 AN: 41522

American (AMR) AF: 0.000852 AC: 13 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000515 AC: 35 AN: 68016

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00188 Hom.: 0

Bravo AF: 0.00286

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.52
DANN	Benign	0.32
PhyloP100		-0.75
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000021
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: rs34799325; hg19: chr11-102586174;