rs2187247

Variant names:

• chr21-42919268-T-A
• rs2187247
• NM_001308491.2:c.-262A>T

Your query was ambiguous. Multiple possible variants found:

• chr21-42919268-T-A
• chr21-42919268-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001308491.2(ERVH48-1):​c.-262A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000897 in 111,422 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 30)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: ERVH48-1 NM_001308491.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.806
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERVH48-1	NM_001308491.2	c.-262A>T		5_prime_UTR_variant	Exon 2 of 2	ENST00000447535.2	NP_001295420.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERVH48-1	ENST00000447535.2	c.-262A>T		5_prime_UTR_variant	Exon 2 of 2	1	NM_001308491.2	ENSP00000504647.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000897 AC: 1 AN: 111422 Hom.: 0 Cov.: 0 AF XY: 0.0000170 AC XY: 1 AN XY: 58884

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

African (AFR) AF: 0.00 AC: 0 AN: 3874

American (AMR) AF: 0.00 AC: 0 AN: 5446

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2726

East Asian (EAS) AF: 0.00 AC: 0 AN: 5940

South Asian (SAS) AF: 0.0000574 AC: 1 AN: 17424

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4552

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 442

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65372

Other (OTH) AF: 0.00 AC: 0 AN: 5646

⚠️ 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 Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.0
DANN	Benign	0.20
PhyloP100		-0.81

Splicing

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

Other links and lift over

dbSNP: rs2187247; hg19: chr21-44339378;