rs7810469

Variant names:

• chr7-94668502-G-A
• rs7810469
• ENST00000615790.5:c.*3968G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000615790.5(PEG10):​c.*3968G>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 ENST00000615790.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PEG10	NM_001172437.2	c.*2820G>A		3_prime_UTR_variant	Exon 2 of 2		NP_001165908.1
PEG10	NM_001184961.1	c.*2820G>A		3_prime_UTR_variant	Exon 2 of 2		NP_001171890.1
PEG10	NM_015068.3	c.*2820G>A		3_prime_UTR_variant	Exon 2 of 2		NP_055883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEG10	ENST00000615790.5	c.*3968G>A		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000482653.2
PEG10	ENST00000482108.1	c.*3968G>A		3_prime_UTR_variant	Exon 2 of 2	1		ENSP00000417587.1
PEG10	ENST00000612941.2	c.*2820G>A		3_prime_UTR_variant	Exon 3 of 3	5		ENSP00000478744.2

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

African (AFR) AF: 0.250 AC: 1 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.250 AC: 1 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0681 AC: 992 AN: 14560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0854 AC: 7 AN: 82

Other (OTH) AF: 0.0333 AC: 3 AN: 90

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

African (AFR) AF: 0.0671 AC: 2788 AN: 41538

American (AMR) AF: 0.0824 AC: 1259 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.127 AC: 439 AN: 3470

East Asian (EAS) AF: 0.171 AC: 883 AN: 5172

South Asian (SAS) AF: 0.0449 AC: 217 AN: 4828

European-Finnish (FIN) AF: 0.0671 AC: 711 AN: 10592

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0884 AC: 6011 AN: 68004

Other (OTH) AF: 0.111 AC: 234 AN: 2114

Alfa AF: 0.0877 Hom.: 367

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
PhyloP100		-0.94
Mutation Taster		=100/0	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: rs7810469; hg19: chr7-94297814;