chr16-10532740-AT-A

Variant names:

• chr16-10532740-AT-A
• rs35927182
• NM_001424.6:c.*164delA

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 VariationId 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.

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.*164delA		3_prime_UTR	Exon 5 of 5	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.*164delA		3_prime_UTR	Exon 5 of 5	ENSP00000352540.3	P54851
	EMP2	ENST00000867008.1		c.*164delA		splice_region	Exon 6 of 6	ENSP00000537067.1
	EMP2	ENST00000971799.1		c.*164delA		splice_region	Exon 6 of 6	ENSP00000641858.1

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

African (AFR) AF: 0.677 AC: 1505 AN: 2222

American (AMR) AF: 0.301 AC: 380 AN: 1262

Ashkenazi Jewish (ASJ) AF: 0.306 AC: 1042 AN: 3400

East Asian (EAS) AF: 0.726 AC: 3835 AN: 5280

South Asian (SAS) AF: 0.750 AC: 1875 AN: 2500

European-Finnish (FIN) AF: 0.440 AC: 1198 AN: 2722

Middle Eastern (MID) AF: 0.395 AC: 226 AN: 572

European-Non Finnish (NFE) AF: 0.425 AC: 35907 AN: 84528

Other (OTH) AF: 0.445 AC: 2440 AN: 5480

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

African (AFR) AF: 0.820 AC: 22499 AN: 27448

American (AMR) AF: 0.705 AC: 4945 AN: 7012

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 1415 AN: 2258

East Asian (EAS) AF: 0.822 AC: 2742 AN: 3334

South Asian (SAS) AF: 0.824 AC: 2752 AN: 3338

European-Finnish (FIN) AF: 0.777 AC: 2288 AN: 2944

Middle Eastern (MID) AF: 0.702 AC: 132 AN: 188

European-Non Finnish (NFE) AF: 0.714 AC: 32509 AN: 45554

Other (OTH) AF: 0.721 AC: 900 AN: 1248

Alfa AF: 0.00 Hom.: 0

Asia WGS AF: 0.683 AC: 1753 AN: 2572

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.66
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: rs35927182; hg19: chr16-10626597; COSMIC: COSV63995656; COSMIC: COSV63995656;