rs7258746

Positions:

• chr19-53051066-A-G

Variant summary

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

The NM_001191055.2(ERVV-2):​c.*207A>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 0.396 in 490,842 control chromosomes in the GnomAD database, including 38,762 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 0.37 (10560 hom., cov: 28)
  • Exomes 𝑓: 0.41 (28202 hom.)
• Consequence: ERVV-2 NM_001191055.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554

Genes affected

ERVV-2 (HGNC:39051): (endogenous retrovirus group V member 2, envelope) Many different human endogenous retrovirus (HERV) families are expressed in normal placental tissue at high levels, suggesting that HERVs are functionally important in reproduction. This gene is part of an HERV provirus on human chromosome 19 that has inactivating mutations in the gag and pol genes. This envelope glycoprotein gene appears to have been selectively preserved. The gene's protein product is expressed in the placenta and acts as a syncytin in Old World monkeys, but has lost the fusogenic activity in humans and other primate lineages. [provided by RefSeq, Jun 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 (AMR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERVV-2	NM_001191055.2	c.*207A>G		3_prime_UTR_variant	2/2	ENST00000601417.3	NP_001177984.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERVV-2	ENST00000601417.3	c.*207A>G		3_prime_UTR_variant	2/2	4	NM_001191055.2	ENSP00000472919.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 55233 AN: 149462 Hom.: 10542 Cov.: 28

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.318

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.399

GnomAD4 exome AF: 0.407 AC: 138999 AN: 341282 Hom.: 28202 Cov.: 3 AF XY: 0.404 AC XY: 72287 AN XY: 178956

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.540

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.371

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.425

Gnomad4 OTH exome AF: 0.422

GnomAD4 genome AF: 0.370 AC: 55277 AN: 149560 Hom.: 10560 Cov.: 28 AF XY: 0.369 AC XY: 26883 AN XY: 72816

Gnomad4 AFR AF: 0.282

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.308

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.318

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.400

Alfa AF: 0.393 Hom.: 3069

Bravo AF: 0.379

Asia WGS AF: 0.272 AC: 948 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	3.8
DANN	Benign	0.59

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: rs7258746; hg19: chr19-53554319;