6-149889549-C-T

Variant names:

• chr6-149889549-C-T
• rs9383921
• NM_001394057.1:c.421G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 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 0.37 (11994 hom., cov: 31)
  • Exomes 𝑓: 0.41 (129337 hom.)
• Consequence: RAET1E NM_001394057.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880
• Publications: 30 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAET1E	NM_001394057.1	c.421G>A	p.Ala141Thr	missense_variant	Exon 5 of 6	ENST00000357183.9	NP_001380986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAET1E	ENST00000357183.9	c.421G>A	p.Ala141Thr	missense_variant	Exon 5 of 6	1	NM_001394057.1	ENSP00000349709.4
ENSG00000285991	ENST00000647612.1	n.421G>A		non_coding_transcript_exon_variant	Exon 4 of 15			ENSP00000498179.1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56443 AN: 151758 Hom.: 11988 Cov.: 31

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

GnomAD2 exomes AF: 0.449 AC: 112738 AN: 251310 AF XY: 0.451

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 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.: 46 AF XY: 0.414 AC XY: 300866 AN XY: 727070

African (AFR) AF: 0.190 AC: 6365 AN: 33478

American (AMR) AF: 0.476 AC: 21276 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 11772 AN: 26132

East Asian (EAS) AF: 0.864 AC: 34284 AN: 39698

South Asian (SAS) AF: 0.483 AC: 41659 AN: 86248

European-Finnish (FIN) AF: 0.416 AC: 22232 AN: 53420

Middle Eastern (MID) AF: 0.391 AC: 2256 AN: 5766

European-Non Finnish (NFE) AF: 0.391 AC: 434997 AN: 1111672

Other (OTH) AF: 0.425 AC: 25664 AN: 60390

GnomAD4 genome AF: 0.372 AC: 56488 AN: 151878 Hom.: 11994 Cov.: 31 AF XY: 0.379 AC XY: 28126 AN XY: 74220

African (AFR) AF: 0.203 AC: 8422 AN: 41482

American (AMR) AF: 0.454 AC: 6927 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.465 AC: 1614 AN: 3472

East Asian (EAS) AF: 0.883 AC: 4530 AN: 5130

South Asian (SAS) AF: 0.489 AC: 2351 AN: 4810

European-Finnish (FIN) AF: 0.416 AC: 4377 AN: 10512

Middle Eastern (MID) AF: 0.404 AC: 118 AN: 292

European-Non Finnish (NFE) AF: 0.397 AC: 26959 AN: 67900

Other (OTH) AF: 0.399 AC: 843 AN: 2112

Alfa AF: 0.401 Hom.: 46641

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	T
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	N
LIST_S2	Benign	0.38	T;T;T;T
MetaRNN	Benign	0.0000029	T;T;T;T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.88
PrimateAI	Benign	0.22	T
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	T
GERP RS		-2.1
Varity_R		0.054
gMVP		0.10
Mutation Taster		=100/0	polymorphism (auto)

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: rs9383921; hg19: chr6-150210685; COSMIC: COSV61723287; COSMIC: COSV61723287;