21-42919268-T-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
ERVH48-1	NM_001308491.2	c.-262A>C		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>C		5_prime_UTR_variant	Exon 2 of 2	1	NM_001308491.2	ENSP00000504647.1

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

African (AFR) AF: 0.823 AC: 3182 AN: 3868

American (AMR) AF: 0.329 AC: 1791 AN: 5438

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1305 AN: 2722

East Asian (EAS) AF: 0.193 AC: 1143 AN: 5930

South Asian (SAS) AF: 0.479 AC: 8327 AN: 17374

European-Finnish (FIN) AF: 0.518 AC: 2347 AN: 4534

Middle Eastern (MID) AF: 0.486 AC: 213 AN: 438

European-Non Finnish (NFE) AF: 0.540 AC: 35209 AN: 65198

Other (OTH) AF: 0.522 AC: 2945 AN: 5638

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

African (AFR) AF: 0.820 AC: 33973 AN: 41432

American (AMR) AF: 0.385 AC: 5869 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1679 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1062 AN: 5162

South Asian (SAS) AF: 0.465 AC: 2239 AN: 4816

European-Finnish (FIN) AF: 0.515 AC: 5402 AN: 10498

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.528 AC: 35857 AN: 67904

Other (OTH) AF: 0.510 AC: 1071 AN: 2102

Alfa AF: 0.575 Hom.: 3393

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
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;