Variant 6-149889549-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394057.1(RAET1E):c.421G>A(p.Ala141Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 1,613,406 control chromosomes in the GnomAD database, including 141,331 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.37 ( 11994 hom., cov: 31)

Exomes 𝑓: 0.41 ( 129337 hom. )

Consequence

RAET1E
NM_001394057.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.880

Variant links:

Genes affected

RAET1E (HGNC:16793): (retinoic acid early transcript 1E) This gene belong to the RAET1 family, which consists of major histocompatibility complex (MHC) class I-related genes located in a cluster on chromosome 6q24.2-q25.3. This and RAET1G protein differ from other RAET1 proteins in that they have type I membrane-spanning sequences at their C termini rather than glycosylphosphatidylinositol anchor sequences. This protein functions as a ligand for NKG2D receptor, which is expressed on the surface of several types of immune cells, and is involved in innate and adaptive immune responses. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2011]

RAET1E links:

RAET1E-LRP11 (HGNC:):

RAET1E-LRP11 links:

RAET1E-AS1 (HGNC:48994): (RAET1E antisense RNA 1)

RAET1E-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.9329944E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RAET1E	NM_001394057.1 linkuse as main transcript	c.421G>A	p.Ala141Thr	missense_variant	5/6	ENST00000357183.9
RAET1E-LRP11	NR_182438.1 linkuse as main transcript	n.839G>A		non_coding_transcript_exon_variant	4/15
RAET1E-AS1	NR_045126.1 linkuse as main transcript	n.885+25167C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAET1E	ENST00000357183.9 linkuse as main transcript	c.421G>A	p.Ala141Thr	missense_variant	5/6	1	NM_001394057.1	P2	Q8TD07-1
RAET1E-AS1	ENST00000605899.1 linkuse as main transcript	n.114+3876C>T		intron_variant, non_coding_transcript_variant		5
RAET1E-AS1	ENST00000606915.1 linkuse as main transcript	n.889+25167C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.372

AC:

56443

AN:

151758

Hom.:

11988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.382

Gnomad AMR

AF:

0.454

Gnomad ASJ

AF:

0.465

Gnomad EAS

AF:

0.883

Gnomad SAS

AF:

0.491

Gnomad FIN

AF:

0.416

Gnomad MID

AF:

0.414

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.399

GnomAD3 exomes

AF:

0.449

AC:

112738

AN:

251310

Hom.:

27923

AF XY:

0.451

AC XY:

61312

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.477

Gnomad ASJ exome

AF:

0.455

Gnomad EAS exome

AF:

0.892

Gnomad SAS exome

AF:

0.481

Gnomad FIN exome

AF:

0.421

Gnomad NFE exome

AF:

0.400

Gnomad OTH exome

AF:

0.450

GnomAD4 exome

AF:

0.411

AC:

600505

AN:

1461528

Hom.:

129337

Cov.:

AF XY:

0.414

AC XY:

300866

AN XY:

727070

show subpopulations

Gnomad4 AFR exome

AF:

0.190

Gnomad4 AMR exome

AF:

0.476

Gnomad4 ASJ exome

AF:

0.450

Gnomad4 EAS exome

AF:

0.864

Gnomad4 SAS exome

AF:

0.483

Gnomad4 FIN exome

AF:

0.416

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.425

GnomAD4 genome

AF:

0.372

AC:

56488

AN:

151878

Hom.:

11994

Cov.:

AF XY:

0.379

AC XY:

28126

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.203

Gnomad4 AMR

AF:

0.454

Gnomad4 ASJ

AF:

0.465

Gnomad4 EAS

AF:

0.883

Gnomad4 SAS

AF:

0.489

Gnomad4 FIN

AF:

0.416

Gnomad4 NFE

AF:

0.397

Gnomad4 OTH

AF:

0.399

Alfa

AF:

0.409

Hom.:

23116

Bravo

AF:

0.372

TwinsUK

AF:

0.388

AC:

1437

ALSPAC

AF:

0.379

AC:

1460

ESP6500AA

AF:

0.205

AC:

905

ESP6500EA

AF:

0.401

AC:

3445

ExAC

AF:

0.439

AC:

53327

Asia WGS

AF:

0.618

AC:

2151

AN:

3478

EpiCase

AF:

0.409

EpiControl

AF:

0.408

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.25

DANN

Benign

0.59

DEOGEN2

Benign

0.039

.;T;.;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0014

LIST_S2

Benign

0.38

T;T;T;T

MetaRNN

Benign

0.0000029

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.73

N;N;N;N

REVEL

Benign

0.0070

Sift

Benign

0.39

T;T;T;T

Sift4G

Benign

0.34

T;T;T;T

Polyphen

0.064

B;B;B;.

Vest4

0.048

MPC

0.069

ClinPred

0.0058

GERP RS

-2.1

Varity_R

0.054

gMVP

0.10

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over