Variant 16-10532768-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001424.6(EMP2):c.*137A>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 0.003 in 280,148 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0071 ( 55 hom., cov: 26)

Exomes 𝑓: 0.00022 ( 7 hom. )

Consequence

EMP2
NM_001424.6 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0550

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 -14 ACMG points.

BP4

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

BP6

Variant 16-10532768-T-C is Benign according to our data. Variant chr16-10532768-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1704905.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00706 (804/113912) while in subpopulation AFR AF= 0.025 (763/30526). AF 95% confidence interval is 0.0235. There are 55 homozygotes in gnomad4. There are 376 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 55 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMP2	NM_001424.6 linkuse as main transcript	c.*137A>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.*137A>G		3_prime_UTR_variant	5/5	1	NM_001424.6	ENSP00000352540.3		P54851

Frequencies

GnomAD3 genomes

AF:

0.00707

AC:

805

AN:

113842

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00153

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000286

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000130

Gnomad OTH

AF:

0.00910

GnomAD4 exome

AF:

0.000217

AC:

AN:

166236

Hom.:

Cov.:

AF XY:

0.000171

AC XY:

AN XY:

81826

show subpopulations

Gnomad4 AFR exome

AF:

0.00679

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000755

Gnomad4 OTH exome

AF:

0.000498

GnomAD4 genome

AF:

0.00706

AC:

804

AN:

113912

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

376

AN XY:

54804

show subpopulations

Gnomad4 AFR

AF:

0.0250

Gnomad4 AMR

AF:

0.00152

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000287

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000130

Gnomad4 OTH

AF:

0.00907

Alfa

AF:

0.00590

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 21, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.9

DANN

Benign

0.70

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