rs1504883

chr16-10538088-G-Achr16-10538088-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001424.6(EMP2):c.170-14C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.118

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 -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	UniProt
EMP2	NM_001424.6	c.170-14C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000359543.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMP2	ENST00000359543.8	c.170-14C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001424.6	P1
EMP2	ENST00000536829.1	c.170-14C>T		splice_polypyrimidine_tract_variant, intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65608 AN: 151944 Hom.: 15028 Cov.: 32

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

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.: 51 AF XY: 0.494 AC XY: 358511 AN XY: 726364

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.: 32 AF XY: 0.432 AC XY: 32119 AN XY: 74314

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 11, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	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

Other links and lift over

dbSNP: rs1504883; hg19: chr16-10631945;