16-10532740-AT-A

Position:

• chr16-10532740-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001424.6(EMP2):​c.*164delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (26270 hom., cov: 0)
  • Exomes 𝑓: 0.45 (20248 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.656

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 16-10532740-AT-A is Benign according to our data. Variant chr16-10532740-AT-A is described in ClinVar as [Benign]. Clinvar id is 1243513.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMP2	NM_001424.6	c.*164delA		3_prime_UTR_variant	5/5	ENST00000359543.8	NP_001415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMP2	ENST00000359543	c.*164delA		3_prime_UTR_variant	5/5	1	NM_001424.6	ENSP00000352540.3

Frequencies

GnomAD3 genomes AF: 0.752 AC: 70616 AN: 93896 Hom.: 26273 Cov.: 0

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.823

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.777

Gnomad MID AF: 0.705

Gnomad NFE AF: 0.714

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.448 AC: 48408 AN: 107966 Hom.: 20248 Cov.: 0 AF XY: 0.449 AC XY: 24061 AN XY: 53636

Gnomad4 AFR exome AF: 0.677

Gnomad4 AMR exome AF: 0.301

Gnomad4 ASJ exome AF: 0.306

Gnomad4 EAS exome AF: 0.726

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.440

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.445

GnomAD4 genome AF: 0.752 AC: 70613 AN: 93900 Hom.: 26270 Cov.: 0 AF XY: 0.757 AC XY: 32795 AN XY: 43294

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.777

Gnomad4 NFE AF: 0.714

Gnomad4 OTH AF: 0.721

Asia WGS AF: 0.683 AC: 1753 AN: 2572

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 25, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs35927182; hg19: chr16-10626597;