rs2598108

Positions:

• chr7-37933225-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_017549.5(EPDR1):​c.269+12017A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,208 control chromosomes in the GnomAD database, including 8,476 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 0.33 (8476 hom., cov: 34)
• Consequence: EPDR1 NM_017549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405

Genes affected

EPDR1 (HGNC:17572): (ependymin related 1) The protein encoded by this gene is a type II transmembrane protein that is similar to two families of cell adhesion molecules, the protocadherins and ependymins. This protein may play a role in calcium-dependent cell adhesion. This protein is glycosylated, and the orthologous mouse protein is localized to the lysosome. Alternative splicing results in multiple transcript variants. A related pseudogene has been identified on chromosome 8. [provided by RefSeq, Aug 2011]

ENSG00000290149 (HGNC:):

SFRP4 (HGNC:10778): (secreted frizzled related protein 4) Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPDR1	NM_017549.5	c.269+12017A>C		intron_variant		ENST00000199448.9	NP_060019.2
EPDR1	NM_001242948.2	c.86+11774A>C		intron_variant			NP_001229877.1
EPDR1	NM_001242946.2	c.269+12017A>C		intron_variant			NP_001229875.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPDR1	ENST00000199448.9	c.269+12017A>C		intron_variant		1	NM_017549.5	ENSP00000199448.4
ENSG00000290149	ENST00000476620.1	c.-37-15615A>C		intron_variant		4		ENSP00000425858.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49829 AN: 152090 Hom.: 8469 Cov.: 34

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.327 AC: 49848 AN: 152208 Hom.: 8476 Cov.: 34 AF XY: 0.326 AC XY: 24279 AN XY: 74412

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.339

Alfa AF: 0.340 Hom.: 1366

Bravo AF: 0.326

Asia WGS AF: 0.386 AC: 1342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2598108; hg19: chr7-37972827;