Variant chr6-150022187-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_130900.3(RAET1L):c.142C>T(p.Arg48Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 16)

Exomes 𝑓: 0.000050 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RAET1L
NM_130900.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.176

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 made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11826259).

BP6

Variant 6-150022187-G-A is Benign according to our data. Variant chr6-150022187-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2363348.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAET1L	NM_130900.3 linkuse as main transcript	c.142C>T	p.Arg48Trp	missense_variant	2/5	ENST00000367341.6	NP_570970.2	Q5VY80

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAET1L	ENST00000367341.6 linkuse as main transcript	c.142C>T	p.Arg48Trp	missense_variant	2/5	1	NM_130900.3	ENSP00000356310.1		Q5VY80
RAET1L	ENST00000286380.2 linkuse as main transcript	c.142C>T	p.Arg48Trp	missense_variant	2/4	1		ENSP00000286380.2		Q5VY80

Frequencies

GnomAD3 genomes

AF:

0.0000230

AC:

AN:

130532

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000283

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:

0.00340

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000595

GnomAD3 exomes

AF:

0.0000236

AC:

AN:

127112

Hom.:

AF XY:

0.0000306

AC XY:

AN XY:

65308

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000710

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000404

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000502

AC:

AN:

1455052

Hom.:

Cov.:

AF XY:

0.0000608

AC XY:

AN XY:

724182

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000581

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000542

Gnomad4 OTH exome

AF:

0.0000499

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000230

AC:

AN:

130638

Hom.:

Cov.:

AF XY:

0.0000320

AC XY:

AN XY:

62568

show subpopulations

Gnomad4 AFR

AF:

0.0000282

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:

0.00

Gnomad4 OTH

AF:

0.000588

ExAC

AF:

0.0000131

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

Jun 03, 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

0.15

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.2

DANN

Benign

0.51

DEOGEN2

Benign

0.0099

T;T

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0064

LIST_S2

Benign

0.46

.;T

M_CAP

Benign

0.0019

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.92

PrimateAI

Benign

0.21

PROVEAN

Uncertain

-2.5

D;D

REVEL

Benign

0.030

Sift

Benign

0.11

T;T

Sift4G

Benign

0.084

T;T

Polyphen

0.048

B;B

Vest4

0.14

MutPred

0.65

Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);

MVP

0.030

MPC

2.0

ClinPred

0.017

GERP RS

-2.4

Varity_R

0.21

gMVP

0.29

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