16-10569770-T-G

Variant names:

• chr16-10569770-T-G
• rs2221433
• NM_001424.6:c.-61+10779A>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.-61+10779A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,200 control chromosomes in the GnomAD database, including 44,176 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 0.75 (44176 hom., cov: 32)
• Consequence: EMP2 NM_001424.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 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.-61+10779A>C		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.-61+10779A>C		intron	N/A	ENSP00000352540.3	P54851
	EMP2	ENST00000867006.1		c.-61+10167A>C		intron	N/A	ENSP00000537065.1
	EMP2	ENST00000867008.1		c.-133+10779A>C		intron	N/A	ENSP00000537067.1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114658 AN: 152082 Hom.: 44129 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.754 AC: 114762 AN: 152200 Hom.: 44176 Cov.: 32 AF XY: 0.755 AC XY: 56189 AN XY: 74394

African (AFR) AF: 0.908 AC: 37723 AN: 41552

American (AMR) AF: 0.627 AC: 9583 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.752 AC: 2611 AN: 3470

East Asian (EAS) AF: 0.689 AC: 3559 AN: 5168

South Asian (SAS) AF: 0.785 AC: 3786 AN: 4824

European-Finnish (FIN) AF: 0.761 AC: 8063 AN: 10592

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.693 AC: 47087 AN: 67992

Other (OTH) AF: 0.726 AC: 1534 AN: 2114

Alfa AF: 0.735 Hom.: 5148

Bravo AF: 0.747

Asia WGS AF: 0.747 AC: 2599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.2
DANN	Benign	0.33
PhyloP100		0.20
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: rs2221433; hg19: chr16-10663627;