NM_001424.6:c.*141A>G

Variant names:

• chr16-10532764-T-C
• rs7202721
• NM_001424.6:c.*141A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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 -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 VariationId 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.

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.*141A>G		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.*141A>G		3_prime_UTR	Exon 5 of 5	ENSP00000352540.3	P54851
	EMP2	ENST00000867006.1		c.*141A>G		3_prime_UTR	Exon 5 of 5	ENSP00000537065.1
	EMP2	ENST00000867008.1		c.*141A>G		3_prime_UTR	Exon 6 of 6	ENSP00000537067.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.210 AC: 55 AN: 262

American (AMR) AF: 0.0204 AC: 6 AN: 294

Ashkenazi Jewish (ASJ) AF: 0.0151 AC: 13 AN: 862

East Asian (EAS) AF: 0.155 AC: 44 AN: 284

South Asian (SAS) AF: 0.164 AC: 39 AN: 238

European-Finnish (FIN) AF: 0.0284 AC: 19 AN: 670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 114

European-Non Finnish (NFE) AF: 0.0342 AC: 467 AN: 13656

Other (OTH) AF: 0.0435 AC: 39 AN: 896

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.413 AC: 2831 AN: 6848

American (AMR) AF: 0.0528 AC: 91 AN: 1724

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 11 AN: 680

East Asian (EAS) AF: 0.0685 AC: 10 AN: 146

South Asian (SAS) AF: 0.120 AC: 26 AN: 216

European-Finnish (FIN) AF: 0.0292 AC: 20 AN: 684

Middle Eastern (MID) AF: 0.0357 AC: 1 AN: 28

European-Non Finnish (NFE) AF: 0.0379 AC: 239 AN: 6314

Other (OTH) AF: 0.0833 AC: 22 AN: 264

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: 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
PhyloP100		-0.50
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7202721; hg19: chr16-10626621;