rs7810469

Positions:

• chr7-94668502-G-A

Variant summary

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

The NM_001172437.2(PEG10):​c.*2821G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0817 in 166,954 control chromosomes in the GnomAD database, including 627 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 0.083 (593 hom., cov: 32)
  • Exomes 𝑓: 0.068 (34 hom.)
• Consequence: PEG10 NM_001172437.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936

Genes affected

PEG10 (HGNC:14005): (paternally expressed 10) This is a paternally expressed imprinted gene that is thought to have been derived from the Ty3/Gypsy family of retrotransposons. It contains two overlapping open reading frames, RF1 and RF2, and expresses two proteins: a shorter, gag-like protein (with a CCHC-type zinc finger domain) from RF1; and a longer, gag/pol-like fusion protein (with an additional aspartic protease motif) from RF1/RF2 by -1 translational frameshifting (-1 FS). While -1 FS has been observed in RNA viruses and transposons in both prokaryotes and eukaryotes, this gene represents the first example of -1 FS in a eukaryotic cellular gene. This gene is highly conserved across mammalian species and retains the heptanucleotide (GGGAAAC) and pseudoknot elements required for -1 FS. It is expressed in adult and embryonic tissues (most notably in placenta) and reported to have a role in cell proliferation, differentiation and apoptosis. Overexpression of this gene has been associated with several malignancies, such as hepatocellular carcinoma and B-cell lymphocytic leukemia. Knockout mice lacking this gene showed early embryonic lethality with placental defects, indicating the importance of this gene in embryonic development. Additional isoforms resulting from alternatively spliced transcript variants, and use of upstream non-AUG (CUG) start codon have been reported for this gene. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEG10	NM_001172437.2	c.*2821G>A		3_prime_UTR_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEG10	ENST00000482108.1	c.*3968G>A		3_prime_UTR_variant	2/2	1		A2
PEG10	ENST00000615790.5	c.*3968G>A		3_prime_UTR_variant	2/2	1		A2
PEG10	ENST00000612941.2	c.*2820G>A		3_prime_UTR_variant	3/3	5		A2

Frequencies

GnomAD3 genomes AF: 0.0830 AC: 12622 AN: 152092 Hom.: 590 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.0827

Gnomad ASJ AF: 0.127

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.0447

Gnomad FIN AF: 0.0671

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.0681 AC: 1004 AN: 14746 Hom.: 34 Cov.: 0 AF XY: 0.0677 AC XY: 474 AN XY: 6998

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.0681

Gnomad4 NFE exome AF: 0.0854

Gnomad4 OTH exome AF: 0.0333

GnomAD4 genome AF: 0.0830 AC: 12636 AN: 152208 Hom.: 593 Cov.: 32 AF XY: 0.0813 AC XY: 6051 AN XY: 74406

Gnomad4 AFR AF: 0.0671

Gnomad4 AMR AF: 0.0824

Gnomad4 ASJ AF: 0.127

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.0449

Gnomad4 FIN AF: 0.0671

Gnomad4 NFE AF: 0.0884

Gnomad4 OTH AF: 0.111

Alfa AF: 0.0853 Hom.: 211

Bravo AF: 0.0847

Asia WGS AF: 0.128 AC: 446 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.26
DANN	Benign	0.68

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: rs7810469; hg19: chr7-94297814;