rs1504883

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001424.6(EMP2):c.170-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,612,274 control chromosomes in the GnomAD database, including 197,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15027 hom., cov: 32)

Exomes 𝑓: 0.50 ( 182721 hom. )

Consequence

EMP2
NM_001424.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.118

Publications

6 publications found

Variant links:

Genes affected

EMP2 (HGNC:3334): (epithelial membrane protein 2) This gene encodes a tetraspan protein of the PMP22/EMP family. The encoded protein regulates cell membrane composition. It has been associated with various functions including endocytosis, cell signaling, cell proliferation, cell migration, cell adhesion, cell death, cholesterol homeostasis, urinary albumin excretion, and embryo implantation. It is known to negatively regulate caveolin-1, a scaffolding protein which is the main component of the caveolae plasma membrane invaginations found in most cell types. Through activation of PTK2 it positively regulates vascular endothelial growth factor A. It also modulates the function of specific integrin isomers in the plasma membrane. Up-regulation of this gene has been linked to cancer progression in multiple different tissues. Mutations in this gene have been associated with nephrotic syndrome type 10 (NPHS10). [provided by RefSeq, Mar 2015]

EMP2 Gene-Disease associations (from GenCC):

nephrotic syndrome, type 10
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
familial idiopathic steroid-resistant nephrotic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 16-10538088-G-A is Benign according to our data. Variant chr16-10538088-G-A is described in ClinVar as Benign. ClinVar VariationId is 258093.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMP2	NM_001424.6 link	c.170-14C>T		intron_variant	Intron 3 of 4	ENST00000359543.8	NP_001415.1	P54851Q7Z4B3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMP2	ENST00000359543.8 link	c.170-14C>T		intron_variant	Intron 3 of 4	1	NM_001424.6	ENSP00000352540.3		P54851
EMP2	ENST00000536829.1 link	c.170-14C>T		intron_variant	Intron 3 of 4	2		ENSP00000445712.1		P54851

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65608

AN:

151944

Hom.:

15028

Cov.:

show subpopulations

Gnomad AFR

AF:

0.275

Gnomad AMI

AF:

0.722

Gnomad AMR

AF:

0.430

Gnomad ASJ

AF:

0.341

Gnomad EAS

AF:

0.558

Gnomad SAS

AF:

0.391

Gnomad FIN

AF:

0.526

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.507

Gnomad OTH

AF:

0.439

GnomAD2 exomes

AF:

0.463

AC:

115846

AN:

250346

AF XY:

0.463

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.347

Gnomad EAS exome

AF:

0.567

Gnomad FIN exome

AF:

0.537

Gnomad NFE exome

AF:

0.504

Gnomad OTH exome

AF:

0.479

GnomAD4 exome

AF:

0.496

AC:

724696

AN:

1460212

Hom.:

182721

Cov.:

AF XY:

0.494

AC XY:

358511

AN XY:

726364

show subpopulations

African (AFR)

AF:

0.265

AC:

8873

AN:

33440

American (AMR)

AF:

0.422

AC:

18875

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.342

AC:

8927

AN:

26124

East Asian (EAS)

AF:

0.561

AC:

22278

AN:

39692

South Asian (SAS)

AF:

0.386

AC:

33280

AN:

86184

European-Finnish (FIN)

AF:

0.537

AC:

28602

AN:

53246

Middle Eastern (MID)

AF:

0.346

AC:

1744

AN:

5040

European-Non Finnish (NFE)

AF:

0.516

AC:

573634

AN:

1111534

Other (OTH)

AF:

0.473

AC:

28483

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

19256

38512

57768

77024

96280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16468

32936

49404

65872

82340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.432

AC:

65639

AN:

152062

Hom.:

15027

Cov.:

AF XY:

0.432

AC XY:

32119

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.275

AC:

11407

AN:

41464

American (AMR)

AF:

0.430

AC:

6579

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.341

AC:

1184

AN:

3472

East Asian (EAS)

AF:

0.558

AC:

2885

AN:

5166

South Asian (SAS)

AF:

0.390

AC:

1880

AN:

4818

European-Finnish (FIN)

AF:

0.526

AC:

5564

AN:

10582

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.507

AC:

34442

AN:

67960

Other (OTH)

AF:

0.437

AC:

923

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1863

3726

5589

7452

9315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

598

1196

1794

2392

2990

<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:

0.470

Hom.:

6945

Bravo

AF:

0.421

Asia WGS

AF:

0.460

AC:

1599

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nephrotic syndrome, type 10

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.6

(source)

DANN

Benign

0.59

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over