19-53050086-C-G

Variant names:

• chr19-53050086-C-G
• rs200390313
• NM_001191055.2:c.835C>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001191055.2(ERVV-2):​c.835C>G​(p.Pro279Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (25 hom., cov: 21)
  • Exomes 𝑓: 0.0087 (1258 hom.)
  • Failed GnomAD Quality Control
• Consequence: ERVV-2 NM_001191055.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.637
• Publications: 2 publications found

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]

ZNF702P (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006170988).
• BP6: Variant 19-53050086-C-G is Benign according to our data. Variant chr19-53050086-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3090403.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001191055.2. 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
	ERVV-2	NM_001191055.2	MANE Select	c.835C>G	p.Pro279Ala	missense	Exon 2 of 2	NP_001177984.1	B6SEH9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERVV-2	ENST00000601417.3	TSL:4 MANE Select	c.835C>G	p.Pro279Ala	missense	Exon 2 of 2	ENSP00000472919.1	B6SEH9
	ZNF702P	ENST00000816847.1		n.382+6480G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1686 AN: 134170 Hom.: 25 Cov.: 21

Gnomad AFR AF: 0.00375

Gnomad AMI AF: 0.0125

Gnomad AMR AF: 0.00892

Gnomad ASJ AF: 0.0142

Gnomad EAS AF: 0.0305

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.00884

Gnomad MID AF: 0.0393

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0126

GnomAD2 exomes AF: 0.00710 AC: 893 AN: 125702 AF XY: 0.00705

Gnomad AFR exome AF: 0.00353

Gnomad AMR exome AF: 0.00640

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.0121

Gnomad FIN exome AF: 0.00255

Gnomad NFE exome AF: 0.00698

Gnomad OTH exome AF: 0.00909

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00873 AC: 11322 AN: 1296826 Hom.: 1258 Cov.: 33 AF XY: 0.00948 AC XY: 6063 AN XY: 639778

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

African (AFR) AF: 0.00389 AC: 115 AN: 29552

American (AMR) AF: 0.00924 AC: 309 AN: 33454

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 315 AN: 23708

East Asian (EAS) AF: 0.0251 AC: 812 AN: 32374

South Asian (SAS) AF: 0.0196 AC: 1429 AN: 73030

European-Finnish (FIN) AF: 0.0167 AC: 535 AN: 32098

Middle Eastern (MID) AF: 0.0132 AC: 69 AN: 5236

European-Non Finnish (NFE) AF: 0.00696 AC: 7051 AN: 1013188

Other (OTH) AF: 0.0127 AC: 687 AN: 54186

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0125 AC: 1679 AN: 134266 Hom.: 25 Cov.: 21 AF XY: 0.0120 AC XY: 783 AN XY: 65498

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

African (AFR) AF: 0.00373 AC: 136 AN: 36424

American (AMR) AF: 0.00883 AC: 117 AN: 13252

Ashkenazi Jewish (ASJ) AF: 0.0142 AC: 44 AN: 3106

East Asian (EAS) AF: 0.0301 AC: 140 AN: 4650

South Asian (SAS) AF: 0.0365 AC: 143 AN: 3920

European-Finnish (FIN) AF: 0.00884 AC: 84 AN: 9498

Middle Eastern (MID) AF: 0.0352 AC: 9 AN: 256

European-Non Finnish (NFE) AF: 0.0161 AC: 972 AN: 60428

Other (OTH) AF: 0.0124 AC: 23 AN: 1854

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00828 Hom.: 23

ExAC AF: 0.00286 AC: 39

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.31
DANN	Benign	0.53
DEOGEN2	Benign	0.0058	T
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.0062	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-0.64
PrimateAI	Benign	0.36	T
Sift4G	Pathogenic	0.0	D
Vest4		0.10
MVP		0.14
GERP RS		0.42
Varity_R		0.032
gMVP		0.20
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs200390313; hg19: chr19-53553339; COSMIC: COSV74153509;