rs16879765

Variant names:

• chr7-37949493-C-T
• rs16879765
• NM_017549.5:c.478+445C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017549.5(EPDR1):​c.478+445C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,160 control chromosomes in the GnomAD database, including 1,334 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 0.13 (1334 hom., cov: 32)
• Consequence: EPDR1 NM_017549.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60
• Publications: 25 publications found

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]

SFRP4 Gene-Disease associations (from GenCC):

• Pyle disease

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPDR1	NM_017549.5	c.478+445C>T		intron_variant	Intron 2 of 2	ENST00000199448.9	NP_060019.2
EPDR1	NM_001242948.2	c.295+445C>T		intron_variant	Intron 2 of 2		NP_001229877.1
EPDR1	NM_001242946.2	c.270-707C>T		intron_variant	Intron 1 of 1		NP_001229875.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPDR1	ENST00000199448.9	c.478+445C>T		intron_variant	Intron 2 of 2	1	NM_017549.5	ENSP00000199448.4
ENSG00000290149	ENST00000476620.1	c.172+445C>T		intron_variant	Intron 3 of 3	4		ENSP00000425858.1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19708 AN: 152040 Hom.: 1328 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0973

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.130 AC: 19737 AN: 152160 Hom.: 1334 Cov.: 32 AF XY: 0.133 AC XY: 9883 AN XY: 74380

African (AFR) AF: 0.159 AC: 6590 AN: 41490

American (AMR) AF: 0.152 AC: 2324 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3470

East Asian (EAS) AF: 0.0972 AC: 503 AN: 5176

South Asian (SAS) AF: 0.128 AC: 618 AN: 4822

European-Finnish (FIN) AF: 0.142 AC: 1502 AN: 10580

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7308 AN: 68012

Other (OTH) AF: 0.134 AC: 284 AN: 2114

Alfa AF: 0.113 Hom.: 4527

Bravo AF: 0.131

Asia WGS AF: 0.112 AC: 389 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.10
DANN	Benign	0.27
PhyloP100		-2.6
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: rs16879765; hg19: chr7-37989095;