rs2187247

Positions:

• chr21-42919268-T-G

Variant summary

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

The NM_001308491.2(ERVH48-1):​c.-262A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 262,970 control chromosomes in the GnomAD database, including 42,940 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 0.58 (27552 hom., cov: 30)
  • Exomes 𝑓: 0.51 (15388 hom.)
• Consequence: ERVH48-1 NM_001308491.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806

Genes affected

ERVH48-1 (HGNC:17216): (endogenous retrovirus group 48 member 1, envelope) Many different endogenous retrovirus families are expressed in normal placental tissue at high levels, suggesting that endogenous retroviruses are functionally important in reproduction. This gene is part of an endogenous retrovirus provirus that has placenta specific expression. The protein encoded has the characteristics of a retroviral envelope protein but is truncated and lacks the transmembrane domain. The protein inhibits cell fusion by competing with syncytin-1 for binding to a cell receptor. [provided by RefSeq, May 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ERVH48-1	NM_001308491.2	c.-262A>C		5_prime_UTR_variant	2/2	ENST00000447535.2	NP_001295420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ERVH48-1	ENST00000447535.2	c.-262A>C		5_prime_UTR_variant	2/2	1	NM_001308491.2	ENSP00000504647	P1

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87731 AN: 151708 Hom.: 27505 Cov.: 30

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.561

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.528

Gnomad OTH AF: 0.512

GnomAD4 exome AF: 0.508 AC: 56462 AN: 111140 Hom.: 15388 Cov.: 0 AF XY: 0.502 AC XY: 29485 AN XY: 58724

Gnomad4 AFR exome AF: 0.823

Gnomad4 AMR exome AF: 0.329

Gnomad4 ASJ exome AF: 0.479

Gnomad4 EAS exome AF: 0.193

Gnomad4 SAS exome AF: 0.479

Gnomad4 FIN exome AF: 0.518

Gnomad4 NFE exome AF: 0.540

Gnomad4 OTH exome AF: 0.522

GnomAD4 genome AF: 0.578 AC: 87832 AN: 151830 Hom.: 27552 Cov.: 30 AF XY: 0.570 AC XY: 42249 AN XY: 74174

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.206

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.528

Gnomad4 OTH AF: 0.510

Alfa AF: 0.564 Hom.: 3129

Bravo AF: 0.575

Asia WGS AF: 0.338 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.1
DANN	Benign	0.52

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2187247; hg19: chr21-44339378;