16-10538088-G-A

Variant names:

• chr16-10538088-G-A
• rs1504883
• NM_001424.6:c.170-14C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.118
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• nephrotic syndrome, type 10

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001424.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMP2	NM_001424.6	MANE Select	c.170-14C>T		intron	N/A	NP_001415.1	P54851

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMP2	ENST00000359543.8	TSL:1 MANE Select	c.170-14C>T		intron	N/A	ENSP00000352540.3	P54851
	EMP2	ENST00000536829.1	TSL:2	c.170-14C>T		intron	N/A	ENSP00000445712.1	P54851
	EMP2	ENST00000867006.1		c.170-14C>T		intron	N/A	ENSP00000537065.1

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

GnomAD2 exomes AF: 0.463 AC: 115846 AN: 250346 AF XY: 0.463

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 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

African (AFR) AF: 0.265 AC: 8873 AN: 33440

American (AMR) AF: 0.422 AC: 18875 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 8927 AN: 26124

East Asian (EAS) AF: 0.561 AC: 22278 AN: 39692

South Asian (SAS) AF: 0.386 AC: 33280 AN: 86184

European-Finnish (FIN) AF: 0.537 AC: 28602 AN: 53246

Middle Eastern (MID) AF: 0.346 AC: 1744 AN: 5040

European-Non Finnish (NFE) AF: 0.516 AC: 573634 AN: 1111534

Other (OTH) AF: 0.473 AC: 28483 AN: 60256

GnomAD4 genome AF: 0.432 AC: 65639 AN: 152062 Hom.: 15027 Cov.: 32 AF XY: 0.432 AC XY: 32119 AN XY: 74314

African (AFR) AF: 0.275 AC: 11407 AN: 41464

American (AMR) AF: 0.430 AC: 6579 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1184 AN: 3472

East Asian (EAS) AF: 0.558 AC: 2885 AN: 5166

South Asian (SAS) AF: 0.390 AC: 1880 AN: 4818

European-Finnish (FIN) AF: 0.526 AC: 5564 AN: 10582

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34442 AN: 67960

Other (OTH) AF: 0.437 AC: 923 AN: 2112

Alfa AF: 0.470 Hom.: 6945

Bravo AF: 0.421

Asia WGS AF: 0.460 AC: 1599 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Nephrotic syndrome, type 10 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.59
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1504883; hg19: chr16-10631945;