rs6575805

Variant names:

• chr14-100882680-A-G
• rs6575805
• NM_001134888.3:c.2109T>C
• RTL1 p.Phe703Phe

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001134888.3(RTL1):​c.2109T>C​(p.Phe703Phe) 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
• Publications: 21 publications found

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]

MIR493HG (HGNC:55978): (MIR493 cluster host gene)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134888.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTL1	NM_001134888.3	MANE Select	c.2109T>C	p.Phe703Phe	synonymous	Exon 4 of 4	NP_001128360.1	A6NKG5
	RTL1	NM_001425285.1		c.2109T>C	p.Phe703Phe	synonymous	Exon 3 of 3	NP_001412214.1	A6NKG5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTL1	ENST00000649591.1	MANE Select	c.2109T>C	p.Phe703Phe	synonymous	Exon 4 of 4	ENSP00000497482.1	A6NKG5
	MIR493HG	ENST00000637474.1	TSL:5	n.109-6969A>G		intron	N/A

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

GnomAD2 exomes AF: 0.665 AC: 105114 AN: 158068 AF XY: 0.662

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 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

African (AFR) AF: 0.839 AC: 26513 AN: 31600

American (AMR) AF: 0.482 AC: 17218 AN: 35702

Ashkenazi Jewish (ASJ) AF: 0.794 AC: 19993 AN: 25180

East Asian (EAS) AF: 0.452 AC: 16149 AN: 35736

South Asian (SAS) AF: 0.504 AC: 39964 AN: 79236

European-Finnish (FIN) AF: 0.804 AC: 39712 AN: 49396

Middle Eastern (MID) AF: 0.659 AC: 3757 AN: 5700

European-Non Finnish (NFE) AF: 0.764 AC: 824621 AN: 1079042

Other (OTH) AF: 0.724 AC: 42014 AN: 58070

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

African (AFR) AF: 0.835 AC: 34644 AN: 41472

American (AMR) AF: 0.581 AC: 8880 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2760 AN: 3470

East Asian (EAS) AF: 0.460 AC: 2375 AN: 5162

South Asian (SAS) AF: 0.505 AC: 2428 AN: 4808

European-Finnish (FIN) AF: 0.805 AC: 8510 AN: 10568

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52110 AN: 67964

Other (OTH) AF: 0.731 AC: 1539 AN: 2106

Alfa AF: 0.751 Hom.: 77974

Bravo AF: 0.738

Asia WGS AF: 0.504 AC: 1753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.19
DANN	Benign	0.35
PhyloP100		-2.5
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6575805;

hg19: chr14-101349017;

COSMIC: COSV66016844;

COSMIC: COSV66016844;