Variant 14-100881251-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001134888.3(RTL1):c.3538T>C(p.Ser1180Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000747 in 1,549,640 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00080 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00074 ( 4 hom. )

Consequence

RTL1
NM_001134888.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.536

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0065122247).

BP6

Variant 14-100881251-A-G is Benign according to our data. Variant chr14-100881251-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3156882.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RTL1	NM_001134888.3 link	c.3538T>C	p.Ser1180Pro	missense_variant	4/4	ENST00000649591.1	NP_001128360.1	A6NKG5B9EK54
RTL1	NM_001425285.1 link	c.3538T>C	p.Ser1180Pro	missense_variant	3/3		NP_001412214.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RTL1	ENST00000649591.1 link	c.3538T>C	p.Ser1180Pro	missense_variant	4/4		NM_001134888.3	ENSP00000497482.1		A6NKG5
MIR493HG	ENST00000637474.1 link	n.109-8398A>G		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000803

AC:

122

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000389

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000706

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00117

AC:

182

AN:

155798

Hom.:

AF XY:

0.00102

AC XY:

AN XY:

82488

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00466

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000804

Gnomad OTH exome

AF:

0.00432

GnomAD4 exome

AF:

0.000741

AC:

1036

AN:

1397504

Hom.:

Cov.:

AF XY:

0.000720

AC XY:

496

AN XY:

689148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000950

Gnomad4 AMR exome

AF:

0.00505

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000208

Gnomad4 NFE exome

AF:

0.000738

Gnomad4 OTH exome

AF:

0.000966

GnomAD4 genome

AF:

0.000802

AC:

122

AN:

152136

Hom.:

Cov.:

AF XY:

0.000955

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000390

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000738

Hom.:

Bravo

AF:

0.00123

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000223

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

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

0.051

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.48

DANN

Benign

0.30

DEOGEN2

Benign

0.037

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0040

LIST_S2

Benign

0.28

.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0065

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.42

N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.88

.;N

REVEL

Benign

0.0090

Sift

Benign

0.33

.;T

Sift4G

Benign

0.36

.;T

Vest4

0.11

MVP

0.061

MPC

0.75

ClinPred

0.017

GERP RS

-1.8

Varity_R

0.046

gMVP

0.50

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