6-150025396-T-C

Variant names:

• chr6-150025396-T-C
• rs1543547
• NM_130900.3:c.76A>G

Variant summary

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

The NM_130900.3(RAET1L):​c.76A>G​(p.Arg26Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 1,612,468 control chromosomes in the GnomAD database, including 161,832 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 0.45 (15375 hom., cov: 33)
  • Exomes 𝑓: 0.45 (146457 hom.)
• Consequence: RAET1L NM_130900.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 25 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.1800399E-4).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130900.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAET1L	NM_130900.3	MANE Select	c.76A>G	p.Arg26Gly	missense	Exon 1 of 5	NP_570970.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAET1L	ENST00000367341.6	TSL:1 MANE Select	c.76A>G	p.Arg26Gly	missense	Exon 1 of 5	ENSP00000356310.1
	RAET1L	ENST00000286380.2	TSL:1	c.76A>G	p.Arg26Gly	missense	Exon 1 of 4	ENSP00000286380.2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67728 AN: 151996 Hom.: 15360 Cov.: 33

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.444

GnomAD2 exomes AF: 0.421 AC: 105457 AN: 250320 AF XY: 0.422

Gnomad AFR exome AF: 0.478

Gnomad AMR exome AF: 0.388

Gnomad ASJ exome AF: 0.421

Gnomad EAS exome AF: 0.221

Gnomad FIN exome AF: 0.466

Gnomad NFE exome AF: 0.449

Gnomad OTH exome AF: 0.426

GnomAD4 exome AF: 0.446 AC: 650677 AN: 1460354 Hom.: 146457 Cov.: 35 AF XY: 0.445 AC XY: 323021 AN XY: 726460

African (AFR) AF: 0.477 AC: 15949 AN: 33454

American (AMR) AF: 0.388 AC: 17321 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 10901 AN: 26096

East Asian (EAS) AF: 0.262 AC: 10398 AN: 39680

South Asian (SAS) AF: 0.414 AC: 35671 AN: 86164

European-Finnish (FIN) AF: 0.459 AC: 24496 AN: 53346

Middle Eastern (MID) AF: 0.453 AC: 2602 AN: 5742

European-Non Finnish (NFE) AF: 0.457 AC: 507193 AN: 1110886

Other (OTH) AF: 0.434 AC: 26146 AN: 60312

GnomAD4 genome AF: 0.446 AC: 67781 AN: 152114 Hom.: 15375 Cov.: 33 AF XY: 0.443 AC XY: 32925 AN XY: 74376

African (AFR) AF: 0.475 AC: 19696 AN: 41502

American (AMR) AF: 0.407 AC: 6230 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1416 AN: 3470

East Asian (EAS) AF: 0.232 AC: 1196 AN: 5166

South Asian (SAS) AF: 0.420 AC: 2028 AN: 4826

European-Finnish (FIN) AF: 0.465 AC: 4919 AN: 10578

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.454 AC: 30844 AN: 67962

Other (OTH) AF: 0.445 AC: 942 AN: 2116

Alfa AF: 0.443 Hom.: 10337

Bravo AF: 0.442

TwinsUK AF: 0.457 AC: 1696

ALSPAC AF: 0.445 AC: 1716

ESP6500AA AF: 0.474 AC: 2088

ESP6500EA AF: 0.450 AC: 3871

ExAC AF: 0.422 AC: 51216

Asia WGS AF: 0.366 AC: 1272 AN: 3478

EpiCase AF: 0.445

EpiControl AF: 0.450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.40
DANN	Benign	0.18
DEOGEN2	Benign	0.00063	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00038	N
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.00022	T
MetaSVM	Benign	-1.1	T
PhyloP100		-1.3
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.64	N
REVEL	Benign	0.010
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.016
MPC		0.023
ClinPred		0.0033	T
GERP RS		0.43
PromoterAI		0.029	Neutral
Varity_R		0.057
gMVP		0.12
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: rs1543547; hg19: chr6-150346532; COSMIC: COSV53952892;