16-10532774-T-C

Position:

• chr16-10532774-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.*131A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 141,256 control chromosomes in the GnomAD database, including 1,559 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.092 (1559 hom., cov: 27)
  • Exomes 𝑓: 0.14 (8355 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: 1.91

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=-0.81).
• BP6: Variant 16-10532774-T-C is Benign according to our data. Variant chr16-10532774-T-C is described in ClinVar as [Benign]. Clinvar id is 1264243.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMP2	NM_001424.6	c.*131A>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.*131A>G		3_prime_UTR_variant	5/5	1	NM_001424.6	ENSP00000352540.3

Frequencies

GnomAD3 genomes AF: 0.0920 AC: 12991 AN: 141194 Hom.: 1559 Cov.: 27

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.0656

Gnomad AMR AF: 0.0510

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.0719

Gnomad MID AF: 0.153

Gnomad NFE AF: 0.0850

Gnomad OTH AF: 0.0923

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.138 AC: 30964 AN: 223960 Hom.: 8355 Cov.: 5 AF XY: 0.140 AC XY: 15426 AN XY: 110376

Gnomad4 AFR exome AF: 0.119

Gnomad4 AMR exome AF: 0.0696

Gnomad4 ASJ exome AF: 0.190

Gnomad4 EAS exome AF: 0.244

Gnomad4 SAS exome AF: 0.450

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.0919 AC: 12986 AN: 141256 Hom.: 1559 Cov.: 27 AF XY: 0.0945 AC XY: 6451 AN XY: 68230

Gnomad4 AFR AF: 0.0889

Gnomad4 AMR AF: 0.0510

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.156

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.0719

Gnomad4 NFE AF: 0.0850

Gnomad4 OTH AF: 0.0938

Alfa AF: 0.0736 Hom.: 35

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	Dec 29, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.83

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: rs796305673; hg19: chr16-10626631; COSMIC: COSV63996404; COSMIC: COSV63996404;