Variant rs780698489 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001134888.3(RTL1):c.3842G>A(p.Arg1281His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0014 ( 0 hom. )

Consequence

RTL1
NM_001134888.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.675

Variant links:

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]

RTL1 links:

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

MIR493HG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018980682).

BP6

Variant 14-100880947-C-T is Benign according to our data. Variant chr14-100880947-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2242513.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RTL1	NM_001134888.3 link	c.3842G>A	p.Arg1281His	missense_variant	Exon 4 of 4	ENST00000649591.1	NP_001128360.1	A6NKG5B9EK54
RTL1	NM_001425285.1 link	c.3842G>A	p.Arg1281His	missense_variant	Exon 3 of 3		NP_001412214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RTL1	ENST00000649591.1 link	c.3842G>A	p.Arg1281His	missense_variant	Exon 4 of 4		NM_001134888.3	ENSP00000497482.1		A6NKG5
MIR493HG	ENST00000637474.1 link	n.109-8702C>T		intron_variant	Intron 2 of 18	5

Frequencies

GnomAD3 genomes

AF:

0.00272

AC:

AN:

4050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00308

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00355

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000247

AC:

AN:

64842

Hom.:

AF XY:

0.000302

AC XY:

AN XY:

36418

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000722

Gnomad ASJ exome

AF:

0.000239

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000873

Gnomad FIN exome

AF:

0.000161

Gnomad NFE exome

AF:

0.000348

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00140

AC:

114

AN:

81230

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

AN XY:

44404

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000547

Gnomad4 ASJ exome

AF:

0.000516

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000822

Gnomad4 FIN exome

AF:

0.000573

Gnomad4 NFE exome

AF:

0.00231

Gnomad4 OTH exome

AF:

0.00193

GnomAD4 genome

AF:

0.00272

AC:

AN:

4050

Hom.:

Cov.:

AF XY:

0.00229

AC XY:

AN XY:

2184

show subpopulations

Gnomad4 AFR

AF:

0.00308

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00355

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000206

Hom.:

ExAC

AF:

0.0000526

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Aug 10, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.49

.;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.40

.;N

REVEL

Benign

0.040

Sift

Uncertain

0.0040

.;D

Sift4G

Pathogenic

0.0

.;D

Vest4

0.039

MVP

0.067

MPC

0.74

ClinPred

0.055

GERP RS

-0.65

Varity_R

0.040

gMVP

0.064

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over