16-10532807-C-T

Variant names:

• chr16-10532807-C-T
• rs74007148
• NM_001424.6:c.*98G>A

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001424.6(EMP2):​c.*98G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0313 in 203,584 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (28 hom., cov: 22)
  • Exomes 𝑓: 0.042 (45 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0280
• Publications: 2 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP6: Variant 16-10532807-C-T is Benign according to our data. Variant chr16-10532807-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1201301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0786 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.*98G>A		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.*98G>A		3_prime_UTR	Exon 5 of 5	ENSP00000352540.3	P54851
	EMP2	ENST00000867006.1		c.*98G>A		3_prime_UTR	Exon 5 of 5	ENSP00000537065.1
	EMP2	ENST00000867008.1		c.*98G>A		3_prime_UTR	Exon 6 of 6	ENSP00000537067.1

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 2088 AN: 101872 Hom.: 28 Cov.: 22

Gnomad AFR AF: 0.0235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0143

Gnomad ASJ AF: 0.0658

Gnomad EAS AF: 0.00470

Gnomad SAS AF: 0.0156

Gnomad FIN AF: 0.00714

Gnomad MID AF: 0.0703

Gnomad NFE AF: 0.0190

Gnomad OTH AF: 0.0240

GnomAD4 exome AF: 0.0422 AC: 4292 AN: 101668 Hom.: 45 Cov.: 3 AF XY: 0.0412 AC XY: 2252 AN XY: 54700

African (AFR) AF: 0.0426 AC: 149 AN: 3498

American (AMR) AF: 0.0119 AC: 79 AN: 6656

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 306 AN: 1754

East Asian (EAS) AF: 0.00344 AC: 18 AN: 5232

South Asian (SAS) AF: 0.0203 AC: 168 AN: 8284

European-Finnish (FIN) AF: 0.00711 AC: 50 AN: 7032

Middle Eastern (MID) AF: 0.107 AC: 34 AN: 318

European-Non Finnish (NFE) AF: 0.0506 AC: 3268 AN: 64578

Other (OTH) AF: 0.0510 AC: 220 AN: 4316

GnomAD4 genome AF: 0.0205 AC: 2090 AN: 101916 Hom.: 28 Cov.: 22 AF XY: 0.0206 AC XY: 946 AN XY: 45868

African (AFR) AF: 0.0235 AC: 628 AN: 26780

American (AMR) AF: 0.0143 AC: 90 AN: 6312

Ashkenazi Jewish (ASJ) AF: 0.0658 AC: 200 AN: 3038

East Asian (EAS) AF: 0.00470 AC: 14 AN: 2980

South Asian (SAS) AF: 0.0163 AC: 50 AN: 3074

European-Finnish (FIN) AF: 0.00714 AC: 17 AN: 2380

Middle Eastern (MID) AF: 0.0645 AC: 8 AN: 124

European-Non Finnish (NFE) AF: 0.0190 AC: 1049 AN: 55168

Other (OTH) AF: 0.0252 AC: 34 AN: 1348

Alfa AF: 0.00218 Hom.: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	8.0
DANN	Benign	0.75
PhyloP100		-0.028
Mutation Taster		=100/0	polymorphism

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: rs74007148; hg19: chr16-10626664;