chr12-91000519-G-T

Variant names:

• chr12-91000519-G-T
• rs1920751
• NM_004950.5:c.165+1882C>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPYC	NM_004950.5	c.165+1882C>A		intron_variant	Intron 2 of 6	ENST00000261172.8	NP_004941.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPYC	ENST00000261172.8	c.165+1882C>A		intron_variant	Intron 2 of 6	1	NM_004950.5	ENSP00000261172.3
EPYC	ENST00000551767.1	c.165+1882C>A		intron_variant	Intron 2 of 4	3		ENSP00000448272.1
EPYC	ENST00000550203.1	n.69+1882C>A		intron_variant	Intron 1 of 2	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

African (AFR) AF: 0.720 AC: 29831 AN: 41428

American (AMR) AF: 0.798 AC: 12154 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2972 AN: 3466

East Asian (EAS) AF: 0.804 AC: 4135 AN: 5144

South Asian (SAS) AF: 0.748 AC: 3608 AN: 4826

European-Finnish (FIN) AF: 0.907 AC: 9617 AN: 10598

Middle Eastern (MID) AF: 0.815 AC: 238 AN: 292

European-Non Finnish (NFE) AF: 0.865 AC: 58777 AN: 67930

Other (OTH) AF: 0.811 AC: 1712 AN: 2110

Alfa AF: 0.844 Hom.: 27757

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
PhyloP100		-0.28
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: rs1920751; hg19: chr12-91394296;