rs2176771

Positions:

• chr8-88195036-C-A
• chr8-88195036-C-G
• chr8-88195036-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005941.5(MMP16):​c.281+2122G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 151,926 control chromosomes in the GnomAD database, including 33,594 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (33594 hom., cov: 30)
• Consequence: MMP16 NM_005941.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

Genes affected

MMP16 (HGNC:7162): (matrix metallopeptidase 16) 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 encoded protein activates MMP2 by cleavage. This gene was once referred to as MT-MMP2, but was renamed as MT-MMP3 or MMP16. [provided by RefSeq, Oct 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MMP16	NM_005941.5	c.281+2122G>T		intron_variant		ENST00000286614.11	NP_005932.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MMP16	ENST00000286614.11	c.281+2122G>T		intron_variant		1	NM_005941.5	ENSP00000286614	P1
MMP16	ENST00000544227.5	n.281+2122G>T		intron_variant, non_coding_transcript_variant		1
MMP16	ENST00000522726.1	c.332+2122G>T		intron_variant		4		ENSP00000429147
MMP16	ENST00000520568.1	n.331+2122G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97686 AN: 151808 Hom.: 33603 Cov.: 30

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.429

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.791

Gnomad OTH AF: 0.642

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.643 AC: 97699 AN: 151926 Hom.: 33594 Cov.: 30 AF XY: 0.638 AC XY: 47371 AN XY: 74232

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.686

Gnomad4 EAS AF: 0.430

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.791

Gnomad4 OTH AF: 0.634

Alfa AF: 0.754 Hom.: 87341

Bravo AF: 0.613

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.37
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs2176771; hg19: chr8-89207265;