Genetic Variant NM_017549.5:c.269+12017A>C (chr7-37933225-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.405

Publications

6 publications found

Variant links:

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]

EPDR1 links:

ENSG00000290149 (HGNC:):

ENSG00000290149 links:

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

SFRP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
EPDR1	NM_017549.5 link	c.269+12017A>C	intron_variant	Intron 1 of 2	ENST00000199448.9	NP_060019.2	Q9UM22-1Q96J80
EPDR1	NM_001242948.2 link	c.86+11774A>C	intron_variant	Intron 1 of 2		NP_001229877.1	Q9UM22-3
EPDR1	NM_001242946.2 link	c.269+12017A>C	intron_variant	Intron 1 of 1		NP_001229875.2	Q9UM22-2Q96J80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPDR1	ENST00000199448.9 link	c.269+12017A>C		intron_variant	Intron 1 of 2	1	NM_017549.5	ENSP00000199448.4		Q9UM22-1
ENSG00000290149	ENST00000476620.1 link	c.-37-15615A>C		intron_variant	Intron 2 of 3	4		ENSP00000425858.1		D6RIH7

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49829

AN:

152090

Hom.:

8469

Cov.:

show subpopulations

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.:

AF XY:

0.326

AC XY:

24279

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.250

AC:

10394

AN:

41538

American (AMR)

AF:

0.341

AC:

5212

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1557

AN:

3472

East Asian (EAS)

AF:

0.361

AC:

1874

AN:

5188

South Asian (SAS)

AF:

0.458

AC:

2208

AN:

4822

European-Finnish (FIN)

AF:

0.296

AC:

3134

AN:

10584

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.358

AC:

24313

AN:

67998

Other (OTH)

AF:

0.339

AC:

715

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1805

3610

5416

7221

9026

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.336

Hom.:

1387

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

(source)

DANN

Benign

0.69

PhyloP100

0.41

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over