rs6498068

chr16-10536920-C-Achr16-10536920-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001424.6(EMP2):c.316+1008G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,104 control chromosomes in the GnomAD database, including 48,155 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.79 (48155 hom., cov: 32)
• Consequence: EMP2 NM_001424.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EMP2	NM_001424.6	c.316+1008G>T		intron_variant		ENST00000359543.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EMP2	ENST00000359543.8	c.316+1008G>T		intron_variant		1	NM_001424.6	P1
EMP2	ENST00000536829.1	c.316+1008G>T		intron_variant		2		P1

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120464 AN: 151986 Hom.: 48112 Cov.: 32

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.865

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.813

Gnomad FIN AF: 0.765

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.760

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.793 AC: 120562 AN: 152104 Hom.: 48155 Cov.: 32 AF XY: 0.791 AC XY: 58830 AN XY: 74334

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.730

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.812

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.762

Alfa AF: 0.774 Hom.: 9498

Bravo AF: 0.794

Asia WGS AF: 0.829 AC: 2880 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.4
Dann	Benign	0.81

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: rs6498068; hg19: chr16-10630777;