16-10532764-T-C

Position:

• chr16-10532764-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001424.6(EMP2):​c.*141A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (300 hom., cov: 0)
  • Exomes 𝑓: 0.039 (95 hom.)
  • Failed GnomAD Quality Control
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.504

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 16-10532764-T-C is Benign according to our data. Variant chr16-10532764-T-C is described in ClinVar as [Benign]. Clinvar id is 1287362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMP2	NM_001424.6	c.*141A>G		3_prime_UTR_variant	5/5	ENST00000359543.8	NP_001415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EMP2	ENST00000359543	c.*141A>G		3_prime_UTR_variant	5/5	1	NM_001424.6	ENSP00000352540.3

Frequencies

GnomAD3 genomes AF: 0.192 AC: 3253 AN: 16962 Hom.: 301 Cov.: 0

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0528

Gnomad ASJ AF: 0.0162

Gnomad EAS AF: 0.0676

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0292

Gnomad MID AF: 0.0333

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0802

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0395 AC: 682 AN: 17276 Hom.: 95 Cov.: 0 AF XY: 0.0389 AC XY: 338 AN XY: 8698

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.0204

Gnomad4 ASJ exome AF: 0.0151

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.0284

Gnomad4 NFE exome AF: 0.0342

Gnomad4 OTH exome AF: 0.0435

GnomAD4 genome AF: 0.192 AC: 3251 AN: 16962 Hom.: 300 Cov.: 0 AF XY: 0.191 AC XY: 1571 AN XY: 8208

Gnomad4 AFR AF: 0.413

Gnomad4 AMR AF: 0.0528

Gnomad4 ASJ AF: 0.0162

Gnomad4 EAS AF: 0.0685

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0292

Gnomad4 NFE AF: 0.0379

Gnomad4 OTH AF: 0.0833

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs7202721; hg19: chr16-10626621;