20-35211477-T-G

Variant names:

• chr20-35211477-T-G
• rs6088765
• NM_001355008.2:c.-102+6335A>C

Variant summary

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

The NM_001355008.2(MMP24-AS1-EDEM2):​c.-102+6335A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,974 control chromosomes in the GnomAD database, including 23,300 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 0.53 (23300 hom., cov: 31)
• Consequence: MMP24-AS1-EDEM2 NM_001355008.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150

Genes affected

MMP24-AS1-EDEM2 (HGNC:):

PROCR (HGNC:9452): (protein C receptor) The protein encoded by this gene is a receptor for activated protein C, a serine protease activated by and involved in the blood coagulation pathway. The encoded protein is an N-glycosylated type I membrane protein that enhances the activation of protein C. Mutations in this gene have been associated with venous thromboembolism and myocardial infarction, as well as with late fetal loss during pregnancy. The encoded protein may also play a role in malarial infection and has been associated with cancer. [provided by RefSeq, Jul 2013]

MMP24OS (HGNC:44421): (MMP24 opposite strand)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MMP24-AS1-EDEM2	NM_001355008.2	c.-102+6335A>C		intron_variant	Intron 4 of 14		NP_001341937.1
PROCR	XM_011528496.2	c.713-4416T>G		intron_variant	Intron 4 of 4		XP_011526798.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PROCR	ENST00000635377.1	c.629-4416T>G		intron_variant	Intron 3 of 3	5		ENSP00000489117.1
PROCR	ENST00000634509.1	c.95-4416T>G		intron_variant	Intron 1 of 1	3		ENSP00000489456.1
MMP24OS	ENST00000635104.1	n.571+5271A>C		intron_variant	Intron 4 of 4	5

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80784 AN: 151856 Hom.: 23251 Cov.: 31

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.507

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.506

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

GnomAD4 genome AF: 0.532 AC: 80882 AN: 151974 Hom.: 23300 Cov.: 31 AF XY: 0.533 AC XY: 39630 AN XY: 74308

Gnomad4 AFR AF: 0.763

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.507

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.512

Alfa AF: 0.446 Hom.: 25396

Bravo AF: 0.529

Asia WGS AF: 0.558 AC: 1942 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.4
DANN	Benign	0.71

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6088765; hg19: chr20-33799280;