6-150020964-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_130900.3(RAET1L):ā€‹c.572T>Cā€‹(p.Ile191Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,614,018 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.00044 ( 0 hom., cov: 32)
Exomes š‘“: 0.0011 ( 1 hom. )

Consequence

RAET1L
NM_130900.3 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.69
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.02178973).
BP6
Variant 6-150020964-A-G is Benign according to our data. Variant chr6-150020964-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2238920.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RAET1LNM_130900.3 linkc.572T>C p.Ile191Thr missense_variant 3/5 ENST00000367341.6 NP_570970.2 Q5VY80

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RAET1LENST00000367341.6 linkc.572T>C p.Ile191Thr missense_variant 3/51 NM_130900.3 ENSP00000356310.1 Q5VY80
RAET1LENST00000286380.2 linkc.572T>C p.Ile191Thr missense_variant 3/41 ENSP00000286380.2 Q5VY80

Frequencies

GnomAD3 genomes
AF:
0.000440
AC:
67
AN:
152136
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
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:
0.000853
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000425
AC:
107
AN:
251492
Hom.:
0
AF XY:
0.000405
AC XY:
55
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.000308
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000381
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000817
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.00107
AC:
1557
AN:
1461882
Hom.:
1
Cov.:
91
AF XY:
0.00102
AC XY:
744
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000479
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.00136
Gnomad4 OTH exome
AF:
0.000348
GnomAD4 genome
AF:
0.000440
AC:
67
AN:
152136
Hom.:
0
Cov.:
32
AF XY:
0.000269
AC XY:
20
AN XY:
74320
show subpopulations
Gnomad4 AFR
AF:
0.000217
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:
0.000853
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000785
Hom.:
0
Bravo
AF:
0.000533
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00151
AC:
13
ExAC
AF:
0.000428
AC:
52
EpiCase
AF:
0.000927
EpiControl
AF:
0.000948

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 submitterclinical testingAmbry GeneticsJan 18, 2022This 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
0.062
BayesDel_addAF
Benign
-0.54
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
0.0050
DANN
Benign
0.17
DEOGEN2
Benign
0.0035
T;T
Eigen
Benign
-1.9
Eigen_PC
Benign
-2.0
FATHMM_MKL
Benign
0.00094
N
LIST_S2
Benign
0.12
.;T
M_CAP
Benign
0.0036
T
MetaRNN
Benign
0.022
T;T
MetaSVM
Benign
-1.0
T
PrimateAI
Benign
0.26
T
PROVEAN
Benign
2.4
N;N
REVEL
Benign
0.047
Sift
Benign
0.41
T;T
Sift4G
Benign
0.59
T;T
Polyphen
0.0
B;B
Vest4
0.17
MVP
0.040
MPC
0.14
ClinPred
0.015
T
GERP RS
-3.4
Varity_R
0.17
gMVP
0.064

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.

Other links and lift over

dbSNP: rs147008347; hg19: chr6-150342100; COSMIC: COSV53953750; API