dbSNP rs3825569: RTL1:p.Glu276Glu (chr14-100883961-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001134888.3(RTL1):c.828A>G(p.Glu276Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,551,280 control chromosomes in the GnomAD database, including 283,868 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27373 hom., cov: 32)

Exomes 𝑓: 0.60 ( 256495 hom. )

Consequence

RTL1
NM_001134888.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.81

Publications

27 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:

MEG8 (HGNC:14574): (maternally expressed 8, small nucleolar RNA host gene) This gene is located in a cluster of imprinted genes on chromosome 14q32.3. It encodes a a non-protein coding transcript that is preferentially expressed from the maternal allele in skeletal muscle, and appears to be coordinately regulated with other imprinted genes in this region. [provided by RefSeq, Oct 2010]

MEG8 links:

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

MIR493HG links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 14-100883961-T-C is Benign according to our data. Variant chr14-100883961-T-C is described in ClinVar as Benign. ClinVar VariationId is 1334333.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.625 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.828A>G	p.Glu276Glu	synonymous	Exon 4 of 4	NP_001128360.1	A6NKG5
	RTL1	NM_001425285.1		c.828A>G	p.Glu276Glu	synonymous	Exon 3 of 3	NP_001412214.1	A6NKG5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RTL1	ENST00000649591.1	MANE Select	c.828A>G	p.Glu276Glu	synonymous	Exon 4 of 4	ENSP00000497482.1	A6NKG5
MEG8	ENST00000699458.1		n.905T>C		non_coding_transcript_exon	Exon 1 of 6
MIR493HG	ENST00000637474.1	TSL:5	n.109-5688T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.594

AC:

90211

AN:

151848

Hom.:

27363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.583

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.703

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.603

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.630

Gnomad OTH

AF:

0.620

GnomAD2 exomes

AF:

0.534

AC:

82194

AN:

153990

AF XY:

0.534

show subpopulations

Gnomad AFR exome

AF:

0.623

Gnomad AMR exome

AF:

0.337

Gnomad ASJ exome

AF:

0.700

Gnomad EAS exome

AF:

0.410

Gnomad FIN exome

AF:

0.605

Gnomad NFE exome

AF:

0.633

Gnomad OTH exome

AF:

0.580

GnomAD4 exome

AF:

0.600

AC:

839811

AN:

1399314

Hom.:

256495

Cov.:

AF XY:

0.595

AC XY:

410957

AN XY:

690160

show subpopulations

African (AFR)

AF:

0.618

AC:

19515

AN:

31598

American (AMR)

AF:

0.355

AC:

12679

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

17657

AN:

25180

East Asian (EAS)

AF:

0.420

AC:

15006

AN:

35736

South Asian (SAS)

AF:

0.402

AC:

31874

AN:

79236

European-Finnish (FIN)

AF:

0.604

AC:

29740

AN:

49224

Middle Eastern (MID)

AF:

0.603

AC:

3433

AN:

5694

European-Non Finnish (NFE)

AF:

0.626

AC:

675100

AN:

1078944

Other (OTH)

AF:

0.600

AC:

34807

AN:

58000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

23660

47321

70981

94642

118302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18080

36160

54240

72320

90400

<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:

0.594

AC:

90255

AN:

151966

Hom.:

27373

Cov.:

AF XY:

0.585

AC XY:

43454

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.616

AC:

25548

AN:

41450

American (AMR)

AF:

0.454

AC:

6936

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.703

AC:

2441

AN:

3470

East Asian (EAS)

AF:

0.414

AC:

2131

AN:

5146

South Asian (SAS)

AF:

0.408

AC:

1963

AN:

4806

European-Finnish (FIN)

AF:

0.603

AC:

6371

AN:

10562

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.630

AC:

42826

AN:

67938

Other (OTH)

AF:

0.615

AC:

1298

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1895

3791

5686

7582

9477

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.614

Hom.:

145152

Bravo

AF:

0.583

Asia WGS

AF:

0.417

AC:

1448

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.046

(source)

DANN

Benign

0.65

PhyloP100

-2.8

Mutation Taster

=100/0

polymorphism (auto)

(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

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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