rs7922546

chr10-125772184-G-A

Variant summary

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

The NM_147191.1(MMP21):c.979+34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,611,146 control chromosomes in the GnomAD database, including 94,374 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 0.30 (7536 hom., cov: 32)
  • Exomes 𝑓: 0.34 (86838 hom.)
• Consequence: MMP21 NM_147191.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.337

Genes affected

MMP21 (HGNC:14357): (matrix metallopeptidase 21) This gene encodes a member of the matrix metalloproteinase family. Proteins in this family are involved in the breakdown of extracellular matrix for both normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, and disease processes, such as asthma and tumor metastasis. The encoded protein may play an important role in embryogenesis, particularly in neuronal cells, as well as in lymphocyte development and survival. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MMP21	NM_147191.1	c.979+34C>T		intron_variant		ENST00000368808.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MMP21	ENST00000368808.3	c.979+34C>T		intron_variant		1	NM_147191.1	P1
MMP21	ENST00000651977.1	c.249-1593C>T		intron_variant
MMP21	ENST00000651834.1	c.181+427C>T		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46351 AN: 151924 Hom.: 7545 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.357

Gnomad EAS AF: 0.164

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.350

Gnomad OTH AF: 0.302

GnomAD3 exomes AF: 0.335 AC: 83753 AN: 250090 Hom.: 14718 AF XY: 0.340 AC XY: 45912 AN XY: 135146

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.351

Gnomad ASJ exome AF: 0.370

Gnomad EAS exome AF: 0.168

Gnomad SAS exome AF: 0.333

Gnomad FIN exome AF: 0.439

Gnomad NFE exome AF: 0.353

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.341 AC: 498078 AN: 1459104 Hom.: 86838 Cov.: 32 AF XY: 0.341 AC XY: 247674 AN XY: 725926

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.346

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.431

Gnomad4 NFE exome AF: 0.348

Gnomad4 OTH exome AF: 0.332

GnomAD4 genome AF: 0.305 AC: 46358 AN: 152042 Hom.: 7536 Cov.: 32 AF XY: 0.310 AC XY: 23050 AN XY: 74300

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.309

Gnomad4 ASJ AF: 0.357

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.350

Gnomad4 OTH AF: 0.302

Alfa AF: 0.341 Hom.: 12700

Bravo AF: 0.291

Asia WGS AF: 0.255 AC: 890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.5
Dann	Benign	0.63

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: rs7922546; hg19: chr10-127460753; COSMIC: COSV64289001;