rs16879765

chr7-37949493-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

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 -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/exons	MANE	UniProt
EPDR1	NM_017549.5	c.478+445C>T		intron_variant		ENST00000199448.9
EPDR1	NM_001242946.2	c.270-707C>T		intron_variant
EPDR1	NM_001242948.2	c.295+445C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPDR1	ENST00000199448.9	c.478+445C>T		intron_variant		1	NM_017549.5	P1
EPDR1	ENST00000423717.1	c.270-707C>T		intron_variant		1
EPDR1	ENST00000425345.1	c.295+445C>T		intron_variant		1
SFRP4	ENST00000447200.2	c.-52-22719G>A		intron_variant		5

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

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.152

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.0972

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.134

Alfa AF: 0.111 Hom.: 2170

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

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: rs16879765; hg19: chr7-37989095;