chr11-102608818-T-C

Variant names:

• chr11-102608818-T-C
• rs1711420
• NM_004771.4:c.811+119A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004771.4(MMP20):​c.811+119A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 1,069,792 control chromosomes in the GnomAD database, including 112,854 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.41 (13439 hom., cov: 34)
  • Exomes 𝑓: 0.46 (99415 hom.)
• Consequence: MMP20 NM_004771.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.36
• Publications: 2 publications found

Genes affected

MMP20 (HGNC:7167): (matrix metallopeptidase 20) Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The protein encoded by this gene degrades amelogenin, the major protein component of dental enamel matrix, and thus thought to play a role in tooth enamel formation. A mutation in this gene, which alters the normal splice pattern and results in premature termination of the encoded protein, has been associated with amelogenesis imperfecta. This gene is part of a cluster of MMP genes located on chromosome 11q22.3. [provided by RefSeq, Aug 2011]

MMP20-AS1 (HGNC:56362): (MMP20 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-102608818-T-C is Benign according to our data. Variant chr11-102608818-T-C is described in ClinVar as [Benign]. Clinvar id is 1221257.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP20	NM_004771.4	c.811+119A>G		intron_variant	Intron 5 of 9	ENST00000260228.3	NP_004762.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MMP20	ENST00000260228.3	c.811+119A>G		intron_variant	Intron 5 of 9	1	NM_004771.4	ENSP00000260228.2
MMP20-AS1	ENST00000542119.2	n.233+1366T>C		intron_variant	Intron 1 of 3	3
MMP20-AS1	ENST00000782665.1	n.233+1366T>C		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63045 AN: 152050 Hom.: 13425 Cov.: 34

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.461 AC: 423464 AN: 917624 Hom.: 99415 AF XY: 0.467 AC XY: 223288 AN XY: 477978

African (AFR) AF: 0.329 AC: 7439 AN: 22620

American (AMR) AF: 0.467 AC: 20037 AN: 42936

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 10504 AN: 22720

East Asian (EAS) AF: 0.436 AC: 16046 AN: 36828

South Asian (SAS) AF: 0.575 AC: 42300 AN: 73584

European-Finnish (FIN) AF: 0.357 AC: 17763 AN: 49732

Middle Eastern (MID) AF: 0.515 AC: 1589 AN: 3088

European-Non Finnish (NFE) AF: 0.462 AC: 288224 AN: 623536

Other (OTH) AF: 0.459 AC: 19562 AN: 42580

GnomAD4 genome AF: 0.415 AC: 63086 AN: 152168 Hom.: 13439 Cov.: 34 AF XY: 0.412 AC XY: 30653 AN XY: 74414

African (AFR) AF: 0.332 AC: 13797 AN: 41538

American (AMR) AF: 0.445 AC: 6795 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1562 AN: 3470

East Asian (EAS) AF: 0.454 AC: 2352 AN: 5182

South Asian (SAS) AF: 0.586 AC: 2826 AN: 4822

European-Finnish (FIN) AF: 0.336 AC: 3557 AN: 10574

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30701 AN: 67982

Other (OTH) AF: 0.454 AC: 958 AN: 2110

Alfa AF: 0.416 Hom.: 1749

Bravo AF: 0.419

Asia WGS AF: 0.546 AC: 1902 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0060
DANN	Benign	0.30
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs1711420; hg19: chr11-102479549; COSMIC: COSV52776695; COSMIC: COSV52776695;