12-91000519-G-T

Position:

• chr12-91000519-G-T

Variant summary

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

The NM_004950.5(EPYC):​c.165+1882C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 151,942 control chromosomes in the GnomAD database, including 50,677 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 0.81 (50677 hom., cov: 31)
• Consequence: EPYC NM_004950.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.277

Genes affected

EPYC (HGNC:3053): (epiphycan) Dermatan sulfate proteoglycan 3 is a member of the small leucine-rich repeat proteoglycan family. This gene is composed of seven exons. It regulates fibrillogenesis by interacting with collagen fibrils and other extracellular matrix proteins. [provided by RefSeq, Jul 2008]

EPYC (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPYC	NM_004950.5	c.165+1882C>A		intron_variant		ENST00000261172.8	NP_004941.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPYC	ENST00000261172.8	c.165+1882C>A		intron_variant		1	NM_004950.5	ENSP00000261172.3
EPYC	ENST00000551767.1	c.165+1882C>A		intron_variant		3		ENSP00000448272.1
EPYC	ENST00000550203.1	n.69+1882C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.815 AC: 123663 AN: 151824 Hom.: 50656 Cov.: 31

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.748

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.818

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.814

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

GnomAD4 genome AF: 0.814 AC: 123729 AN: 151942 Hom.: 50677 Cov.: 31 AF XY: 0.815 AC XY: 60524 AN XY: 74268

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.798

Gnomad4 ASJ AF: 0.857

Gnomad4 EAS AF: 0.804

Gnomad4 SAS AF: 0.748

Gnomad4 FIN AF: 0.907

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.811

Alfa AF: 0.844 Hom.: 24745

Bravo AF: 0.801

Asia WGS AF: 0.762 AC: 2647 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.7
DANN	Benign	0.82

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: rs1920751; hg19: chr12-91394296;