16-10569770-T-G

Variant names:

• chr16-10569770-T-G
• rs2221433
• NM_001424.6:c.-61+10779A>C

Variant summary

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

The NM_001424.6(EMP2):​c.-61+10779A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 152,200 control chromosomes in the GnomAD database, including 44,176 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 0.75 (44176 hom., cov: 32)
• Consequence: EMP2 NM_001424.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EMP2	NM_001424.6	c.-61+10779A>C		intron_variant	Intron 1 of 4	ENST00000359543.8	NP_001415.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EMP2	ENST00000359543.8	c.-61+10779A>C		intron_variant	Intron 1 of 4	1	NM_001424.6	ENSP00000352540.3
EMP2	ENST00000342147.4	n.84+10779A>C		intron_variant	Intron 1 of 1	2

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114658 AN: 152082 Hom.: 44129 Cov.: 32

Gnomad AFR AF: 0.908

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.752

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.785

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.728

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

GnomAD4 genome AF: 0.754 AC: 114762 AN: 152200 Hom.: 44176 Cov.: 32 AF XY: 0.755 AC XY: 56189 AN XY: 74394

Gnomad4 AFR AF: 0.908

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.752

Gnomad4 EAS AF: 0.689

Gnomad4 SAS AF: 0.785

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.726

Alfa AF: 0.735 Hom.: 5148

Bravo AF: 0.747

Asia WGS AF: 0.747 AC: 2599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.2
DANN	Benign	0.33

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: rs2221433; hg19: chr16-10663627;