Variant rs1504883 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
EMP2	NM_001424.6 link	c.170-14C>T		intron_variant		ENST00000359543.8	NP_001415.1	P54851Q7Z4B3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMP2	ENST00000359543.8 link	c.170-14C>T		intron_variant		1	NM_001424.6	ENSP00000352540.3		P54851
EMP2	ENST00000536829.1 link	c.170-14C>T		intron_variant		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

GnomAD3 exomes

AF:

0.463

AC:

115846

AN:

250346

Hom.:

27687

AF XY:

0.463

AC XY:

62638

AN XY:

135306

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 SAS exome

AF:

0.387

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

Gnomad4 AFR exome

AF:

0.265

Gnomad4 AMR exome

AF:

0.422

Gnomad4 ASJ exome

AF:

0.342

Gnomad4 EAS exome

AF:

0.561

Gnomad4 SAS exome

AF:

0.386

Gnomad4 FIN exome

AF:

0.537

Gnomad4 NFE exome

AF:

0.516

Gnomad4 OTH exome

AF:

0.473

GnomAD4 genome

AF:

0.432

AC:

65639

AN:

152062

Hom.:

15027

Cov.:

AF XY:

0.432

AC XY:

32119

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.275

Gnomad4 AMR

AF:

0.430

Gnomad4 ASJ

AF:

0.341

Gnomad4 EAS

AF:

0.558

Gnomad4 SAS

AF:

0.390

Gnomad4 FIN

AF:

0.526

Gnomad4 NFE

AF:

0.507

Gnomad4 OTH

AF:

0.437

Alfa

AF:

0.468

Hom.:

4515

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Nephrotic syndrome, type 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.6

DANN

Benign

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over