6-149889516-C-T

Variant names:

• chr6-149889516-C-T
• rs143655455
• NM_001394057.1:c.454G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001394057.1(RAET1E):​c.454G>A​(p.Ala152Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,614,132 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A152S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00020 (0 hom.)
• Consequence: RAET1E NM_001394057.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.81
• Publications: 3 publications found

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]

ENSG00000285991 (HGNC:):

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

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058784187).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394057.1. 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
	RAET1E	NM_001394057.1	MANE Select	c.454G>A	p.Ala152Thr	missense	Exon 5 of 6	NP_001380986.1	Q8TD07-1
	RAET1E	NM_139165.3		c.454G>A	p.Ala152Thr	missense	Exon 3 of 4	NP_631904.1	Q8TD07-1
	RAET1E	NM_001394056.1		c.454G>A	p.Ala152Thr	missense	Exon 5 of 7	NP_001380985.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAET1E	ENST00000357183.9	TSL:1 MANE Select	c.454G>A	p.Ala152Thr	missense	Exon 5 of 6	ENSP00000349709.4	Q8TD07-1
	RAET1E	ENST00000367363.3	TSL:1	c.346G>A	p.Ala116Thr	missense	Exon 3 of 4	ENSP00000356332.3	Q8TD07-2
	RAET1E	ENST00000532335.5	TSL:1	c.454G>A	p.Ala152Thr	missense	Exon 4 of 5	ENSP00000437067.1	Q8TD07-3

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 238 AN: 152124 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

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: 0.0000147

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.000430 AC: 108 AN: 251418 AF XY: 0.000309

Gnomad AFR exome AF: 0.00572

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000200 AC: 293 AN: 1461890 Hom.: 0 Cov.: 36 AF XY: 0.000184 AC XY: 134 AN XY: 727246

African (AFR) AF: 0.00660 AC: 221 AN: 33480

American (AMR) AF: 0.000313 AC: 14 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.0000333 AC: 37 AN: 1112008

Other (OTH) AF: 0.000265 AC: 16 AN: 60396

GnomAD4 genome AF: 0.00157 AC: 239 AN: 152242 Hom.: 1 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74440

African (AFR) AF: 0.00561 AC: 233 AN: 41542

American (AMR) AF: 0.000196 AC: 3 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000668 Hom.: 0

Bravo AF: 0.00184

ESP6500AA AF: 0.00545 AC: 24

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000601 AC: 73

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Uncertain	0.98
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0099	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.8
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.0	N
REVEL	Benign	0.071
Sift	Benign	0.26	T
Sift4G	Benign	1.0	T
Polyphen		0.98	D
Vest4		0.042
MVP		0.15
MPC		0.083
ClinPred		0.021	T
GERP RS		-5.1
Varity_R		0.045
gMVP		0.097
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs143655455; hg19: chr6-150210652; COSMIC: COSV100593466; COSMIC: COSV100593466;