chr16-10539308-A-G

Variant names:

• chr16-10539308-A-G
• rs11074889
• NM_001424.6:c.170-1234T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001424.6(EMP2):​c.170-1234T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,054 control chromosomes in the GnomAD database, including 50,087 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.81 (50087 hom., cov: 31)
• Consequence: EMP2 NM_001424.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.693
• Publications: 17 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial idiopathic steroid-resistant nephrotic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.848 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMP2	NM_001424.6	MANE Select	c.170-1234T>C		intron	N/A	NP_001415.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EMP2	ENST00000359543.8	TSL:1 MANE Select	c.170-1234T>C		intron	N/A	ENSP00000352540.3
	EMP2	ENST00000536829.1	TSL:2	c.170-1234T>C		intron	N/A	ENSP00000445712.1

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122971 AN: 151936 Hom.: 50045 Cov.: 31

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.742

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.798

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.809 AC: 123068 AN: 152054 Hom.: 50087 Cov.: 31 AF XY: 0.808 AC XY: 60051 AN XY: 74328

African (AFR) AF: 0.733 AC: 30411 AN: 41464

American (AMR) AF: 0.780 AC: 11918 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2521 AN: 3472

East Asian (EAS) AF: 0.833 AC: 4296 AN: 5158

South Asian (SAS) AF: 0.855 AC: 4112 AN: 4808

European-Finnish (FIN) AF: 0.859 AC: 9096 AN: 10594

Middle Eastern (MID) AF: 0.747 AC: 218 AN: 292

European-Non Finnish (NFE) AF: 0.853 AC: 58015 AN: 67980

Other (OTH) AF: 0.800 AC: 1684 AN: 2106

Alfa AF: 0.834 Hom.: 229449

Bravo AF: 0.799

Asia WGS AF: 0.855 AC: 2970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.38
DANN	Benign	0.32
PhyloP100		-0.69
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: rs11074889; hg19: chr16-10633165;