chr14-100880947-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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

Publications

0 publications found

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:

MIR431 (HGNC:32027): (microRNA 431) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR431 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 2242513.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RTL1	NM_001134888.3	MANE Select	c.3842G>A	p.Arg1281His	missense	Exon 4 of 4	NP_001128360.1	A6NKG5
RTL1	NM_001425285.1		c.3842G>A	p.Arg1281His	missense	Exon 3 of 3	NP_001412214.1	A6NKG5
MIR431	NR_029965.1		n.-60C>T		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RTL1	ENST00000649591.1	MANE Select	c.3842G>A	p.Arg1281His	missense	Exon 4 of 4	ENSP00000497482.1	A6NKG5
MIR493HG	ENST00000637474.1	TSL:5	n.109-8702C>T		intron	N/A
MIR431	ENST00000385266.1	TSL:6	n.-60C>T		upstream_gene	N/A

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

GnomAD2 exomes

AF:

0.000247

AC:

AN:

64842

AF XY:

0.000302

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 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

African (AFR)

AF:

0.00

AC:

AN:

1242

American (AMR)

AF:

0.000547

AC:

AN:

3658

Ashkenazi Jewish (ASJ)

AF:

0.000516

AC:

AN:

3876

East Asian (EAS)

AF:

0.00

AC:

AN:

428

South Asian (SAS)

AF:

0.0000822

AC:

AN:

12162

European-Finnish (FIN)

AF:

0.000573

AC:

AN:

15698

Middle Eastern (MID)

AF:

0.00124

AC:

AN:

806

European-Non Finnish (NFE)

AF:

0.00231

AC:

AN:

40766

Other (OTH)

AF:

0.00193

AC:

AN:

2594

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00272

AC:

AN:

4050

Hom.:

Cov.:

AF XY:

0.00229

AC XY:

AN XY:

2184

show subpopulations

African (AFR)

AF:

0.00308

AC:

AN:

650

American (AMR)

AF:

0.00

AC:

AN:

210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

100

East Asian (EAS)

AF:

0.00

AC:

AN:

238

South Asian (SAS)

AF:

0.00

AC:

AN:

126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00355

AC:

AN:

2532

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000206

Hom.:

ExAC

AF:

0.0000526

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.49

M_CAP

Benign

0.032

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.68

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.40

REVEL

Benign

0.040

Sift

Uncertain

0.0040

Sift4G

Pathogenic

0.0

Vest4

0.039

MVP

0.067

MPC

0.74

ClinPred

0.055

GERP RS

-0.65

Varity_R

0.040

gMVP

0.064

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over