16-10532765-T-C

Position:

• chr16-10532765-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001424.6(EMP2):​c.*140A>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 0.00449 in 251,822 control chromosomes in the GnomAD database, including 82 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0095 (67 hom., cov: 25)
  • Exomes 𝑓: 0.00055 (15 hom.)
• Consequence: EMP2 NM_001424.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0550

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=-0.88).
• BP6: Variant 16-10532765-T-C is Benign according to our data. Variant chr16-10532765-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1328635.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00952 (1053/110634) while in subpopulation AFR AF= 0.0316 (901/28482). AF 95% confidence interval is 0.0299. There are 67 homozygotes in gnomad4. There are 498 alleles in male gnomad4 subpopulation. Median coverage is 25. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 67 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EMP2	NM_001424.6	c.*140A>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.*140A>G		3_prime_UTR_variant	5/5	1	NM_001424.6	ENSP00000352540.3

Frequencies

GnomAD3 genomes AF: 0.00949 AC: 1049 AN: 110572 Hom.: 67 Cov.: 25

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00330

Gnomad ASJ AF: 0.00273

Gnomad EAS AF: 0.00586

Gnomad SAS AF: 0.00634

Gnomad FIN AF: 0.000308

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000901

Gnomad OTH AF: 0.0150

GnomAD4 exome AF: 0.000545 AC: 77 AN: 141188 Hom.: 15 Cov.: 3 AF XY: 0.000559 AC XY: 39 AN XY: 69734

Gnomad4 AFR exome AF: 0.00670

Gnomad4 AMR exome AF: 0.000405

Gnomad4 ASJ exome AF: 0.000353

Gnomad4 EAS exome AF: 0.000921

Gnomad4 SAS exome AF: 0.000795

Gnomad4 FIN exome AF: 0.000316

Gnomad4 NFE exome AF: 0.000338

Gnomad4 OTH exome AF: 0.000880

GnomAD4 genome AF: 0.00952 AC: 1053 AN: 110634 Hom.: 67 Cov.: 25 AF XY: 0.00937 AC XY: 498 AN XY: 53158

Gnomad4 AFR AF: 0.0316

Gnomad4 AMR AF: 0.00330

Gnomad4 ASJ AF: 0.00273

Gnomad4 EAS AF: 0.00618

Gnomad4 SAS AF: 0.00635

Gnomad4 FIN AF: 0.000308

Gnomad4 NFE AF: 0.000901

Gnomad4 OTH AF: 0.0149

Alfa AF: 0.00717 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 25, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.71

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: rs1336247924; hg19: chr16-10626622;