dbSNP rs1543547: RAET1L:p.Arg26Gly (chr6-150025396-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_130900.3(RAET1L):c.76A>G(p.Arg26Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,612,468 control chromosomes in the GnomAD database, including 161,832 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.45 ( 15375 hom., cov: 33)

Exomes 𝑓: 0.45 ( 146457 hom. )

Consequence

RAET1L
NM_130900.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.27

Publications

25 publications found

Variant links:

Genes affected

RAET1L (HGNC:16798): (retinoic acid early transcript 1L) RAET1L belongs to the RAET1 family of major histocompatibility complex (MHC) class I-related genes, which are located within a 180-kb cluster on chromosome 6q24.2-q25.3. The REAT1 genes encode glycoproteins that contain extracellular alpha-1 and alpha-2 domains, but they lack the membrane proximal Ig-like alpha-3 domain. Most RAET1 glycoproteins are anchored to the membrane via glycosylphosphatidylinositol (GPI) linkage (Radosavljevic et al., 2002 [PubMed 11827464]).[supplied by OMIM, Mar 2008]

RAET1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.1800399E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAET1L	NM_130900.3 link	c.76A>G	p.Arg26Gly	missense_variant	Exon 1 of 5	ENST00000367341.6	NP_570970.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAET1L	ENST00000367341.6 link	c.76A>G	p.Arg26Gly	missense_variant	Exon 1 of 5	1	NM_130900.3	ENSP00000356310.1
RAET1L	ENST00000286380.2 link	c.76A>G	p.Arg26Gly	missense_variant	Exon 1 of 4	1		ENSP00000286380.2

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67728

AN:

151996

Hom.:

15360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.475

Gnomad AMI

AF:

0.419

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.408

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.465

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.444

GnomAD2 exomes

AF:

0.421

AC:

105457

AN:

250320

AF XY:

0.422

show subpopulations

Gnomad AFR exome

AF:

0.478

Gnomad AMR exome

AF:

0.388

Gnomad ASJ exome

AF:

0.421

Gnomad EAS exome

AF:

0.221

Gnomad FIN exome

AF:

0.466

Gnomad NFE exome

AF:

0.449

Gnomad OTH exome

AF:

0.426

GnomAD4 exome

AF:

0.446

AC:

650677

AN:

1460354

Hom.:

146457

Cov.:

AF XY:

0.445

AC XY:

323021

AN XY:

726460

show subpopulations

African (AFR)

AF:

0.477

AC:

15949

AN:

33454

American (AMR)

AF:

0.388

AC:

17321

AN:

44674

Ashkenazi Jewish (ASJ)

AF:

0.418

AC:

10901

AN:

26096

East Asian (EAS)

AF:

0.262

AC:

10398

AN:

39680

South Asian (SAS)

AF:

0.414

AC:

35671

AN:

86164

European-Finnish (FIN)

AF:

0.459

AC:

24496

AN:

53346

Middle Eastern (MID)

AF:

0.453

AC:

2602

AN:

5742

European-Non Finnish (NFE)

AF:

0.457

AC:

507193

AN:

1110886

Other (OTH)

AF:

0.434

AC:

26146

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

17056

34112

51168

68224

85280

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15220

30440

45660

60880

76100

<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:

0.446

AC:

67781

AN:

152114

Hom.:

15375

Cov.:

AF XY:

0.443

AC XY:

32925

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.475

AC:

19696

AN:

41502

American (AMR)

AF:

0.407

AC:

6230

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.408

AC:

1416

AN:

3470

East Asian (EAS)

AF:

0.232

AC:

1196

AN:

5166

South Asian (SAS)

AF:

0.420

AC:

2028

AN:

4826

European-Finnish (FIN)

AF:

0.465

AC:

4919

AN:

10578

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.454

AC:

30844

AN:

67962

Other (OTH)

AF:

0.445

AC:

942

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1998

3995

5993

7990

9988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.443

Hom.:

10337

Bravo

AF:

0.442

TwinsUK

AF:

0.457

AC:

1696

ALSPAC

AF:

0.445

AC:

1716

ESP6500AA

AF:

0.474

AC:

2088

ESP6500EA

AF:

0.450

AC:

3871

ExAC

AF:

0.422

AC:

51216

Asia WGS

AF:

0.366

AC:

1272

AN:

3478

EpiCase

AF:

0.445

EpiControl

AF:

0.450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.40

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.00063

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00038

LIST_S2

Benign

0.44

.;T

MetaRNN

Benign

0.00022

T;T

MetaSVM

Benign

-1.1

PhyloP100

-1.3

PrimateAI

Benign

0.27

PROVEAN

Benign

0.64

N;N

REVEL

Benign

0.010

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.016

MPC

0.023

ClinPred

0.0033

GERP RS

0.43

PromoterAI

0.029

Neutral

(source)

Varity_R

0.057

gMVP

0.12

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over