rs6575805

Positions:

• chr14-100882680-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001134888.3(RTL1):​c.2109T>C​(p.Phe703=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,551,690 control chromosomes in the GnomAD database, including 429,054 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 0.75 (43792 hom., cov: 31)
  • Exomes 𝑓: 0.74 (385262 hom.)
• Consequence: RTL1 NM_001134888.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

Genes affected

RTL1 (HGNC:14665): (retrotransposon Gag like 1) This gene is a retrotransposon-derived, paternally expressed imprinted gene that is highly expressed at the late fetal stage in both the fetus and placenta. It has an overlapping maternally expressed antisense transcript, which contains several microRNAs targeting the transcripts of this gene through an RNA interference (RNAi) mechanism. This gene is essential for maintenance of the fetal capillaries. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP7: Synonymous conserved (PhyloP=-2.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.828 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RTL1	NM_001134888.3	c.2109T>C	p.Phe703=	synonymous_variant	4/4	ENST00000649591.1
RTL1	XM_047431358.1	c.2109T>C	p.Phe703=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RTL1	ENST00000649591.1	c.2109T>C	p.Phe703=	synonymous_variant	4/4		NM_001134888.3	P1

Frequencies

GnomAD3 genomes AF: 0.751 AC: 114051 AN: 151910 Hom.: 43757 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.738

GnomAD3 exomes AF: 0.665 AC: 105114 AN: 158068 Hom.: 36877 AF XY: 0.662 AC XY: 55282 AN XY: 83474

Gnomad AFR exome AF: 0.838

Gnomad AMR exome AF: 0.464

Gnomad ASJ exome AF: 0.794

Gnomad EAS exome AF: 0.454

Gnomad SAS exome AF: 0.499

Gnomad FIN exome AF: 0.801

Gnomad NFE exome AF: 0.764

Gnomad OTH exome AF: 0.703

GnomAD4 exome AF: 0.736 AC: 1029941 AN: 1399662 Hom.: 385262 Cov.: 84 AF XY: 0.729 AC XY: 503462 AN XY: 690324

Gnomad4 AFR exome AF: 0.839

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.794

Gnomad4 EAS exome AF: 0.452

Gnomad4 SAS exome AF: 0.504

Gnomad4 FIN exome AF: 0.804

Gnomad4 NFE exome AF: 0.764

Gnomad4 OTH exome AF: 0.724

GnomAD4 genome AF: 0.751 AC: 114132 AN: 152028 Hom.: 43792 Cov.: 31 AF XY: 0.743 AC XY: 55193 AN XY: 74318

Gnomad4 AFR AF: 0.835

Gnomad4 AMR AF: 0.581

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.767

Gnomad4 OTH AF: 0.731

Alfa AF: 0.755 Hom.: 58186

Bravo AF: 0.738

Asia WGS AF: 0.504 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.19
DANN	Benign	0.35

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: rs6575805; hg19: chr14-101349017; COSMIC: COSV66016844; COSMIC: COSV66016844;