Variant 16-10532896-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001424.6(EMP2):c.*9A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,467,426 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00018 ( 1 hom., cov: 30)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

EMP2
NM_001424.6 3_prime_UTR

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.174

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

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

BP6

Variant 16-10532896-T-C is Benign according to our data. Variant chr16-10532896-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3055582.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMP2	NM_001424.6 linkuse as main transcript	c.*9A>G		3_prime_UTR_variant	5/5	ENST00000359543.8	NP_001415.1	P54851Q7Z4B3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMP2	ENST00000359543 linkuse as main transcript	c.*9A>G		3_prime_UTR_variant	5/5	1	NM_001424.6	ENSP00000352540.3		P54851
EMP2	ENST00000536829 linkuse as main transcript	c.*9A>G		3_prime_UTR_variant	5/5	2		ENSP00000445712.1		P54851

Frequencies

GnomAD3 genomes

AF:

0.000179

AC:

AN:

151002

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00356

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000133

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000374

AC:

AN:

200498

Hom.:

AF XY:

0.000513

AC XY:

AN XY:

109108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000130

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00301

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000924

Gnomad OTH exome

AF:

0.000442

GnomAD4 exome

AF:

0.000213

AC:

280

AN:

1316314

Hom.:

Cov.:

AF XY:

0.000301

AC XY:

194

AN XY:

644102

show subpopulations

Gnomad4 AFR exome

AF:

0.0000338

Gnomad4 AMR exome

AF:

0.0000314

Gnomad4 ASJ exome

AF:

0.0000454

Gnomad4 EAS exome

AF:

0.0000289

Gnomad4 SAS exome

AF:

0.00359

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000407

Gnomad4 OTH exome

AF:

0.000206

GnomAD4 genome

AF:

0.000179

AC:

AN:

151112

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

AN XY:

73774

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00357

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000133

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000983

Hom.:

Bravo

AF:

0.0000604

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

EMP2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 22, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.1

DANN

Benign

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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