rs41551813

Variant names:

• chr6-29828136-A-T
• rs41551813
• NM_001384290.1:c.163A>T

Variant summary

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

The NM_001384290.1(HLA-G):​c.163A>T​(p.Thr55Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0396 in 1,612,984 control chromosomes in the GnomAD database, including 1,478 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.057 (291 hom., cov: 33)
  • Exomes 𝑓: 0.038 (1187 hom.)
• Consequence: HLA-G NM_001384290.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840
• Publications: 11 publications found

Genes affected

HLA-G (HGNC:4964): (major histocompatibility complex, class I, G) HLA-G belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024591386).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0999 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.163A>T	p.Thr55Ser	missense_variant	Exon 2 of 7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.163A>T	p.Thr55Ser	missense_variant	Exon 2 of 7	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.0570 AC: 8662 AN: 152040 Hom.: 286 Cov.: 33

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0821

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.00753

Gnomad SAS AF: 0.0281

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0358

Gnomad OTH AF: 0.0705

GnomAD2 exomes AF: 0.0457 AC: 11282 AN: 247074 AF XY: 0.0429

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0938

Gnomad ASJ exome AF: 0.0760

Gnomad EAS exome AF: 0.00373

Gnomad FIN exome AF: 0.0117

Gnomad NFE exome AF: 0.0354

Gnomad OTH exome AF: 0.0496

GnomAD4 exome AF: 0.0378 AC: 55273 AN: 1460828 Hom.: 1187 Cov.: 90 AF XY: 0.0375 AC XY: 27281 AN XY: 726776

African (AFR) AF: 0.103 AC: 3458 AN: 33452

American (AMR) AF: 0.0930 AC: 4153 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 2000 AN: 26098

East Asian (EAS) AF: 0.00713 AC: 283 AN: 39686

South Asian (SAS) AF: 0.0375 AC: 3234 AN: 86244

European-Finnish (FIN) AF: 0.0126 AC: 663 AN: 52780

Middle Eastern (MID) AF: 0.0866 AC: 497 AN: 5742

European-Non Finnish (NFE) AF: 0.0345 AC: 38371 AN: 1111806

Other (OTH) AF: 0.0433 AC: 2614 AN: 60366

GnomAD4 genome AF: 0.0570 AC: 8680 AN: 152156 Hom.: 291 Cov.: 33 AF XY: 0.0543 AC XY: 4042 AN XY: 74394

African (AFR) AF: 0.102 AC: 4255 AN: 41512

American (AMR) AF: 0.0826 AC: 1260 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0761 AC: 264 AN: 3470

East Asian (EAS) AF: 0.00755 AC: 39 AN: 5164

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4828

European-Finnish (FIN) AF: 0.0106 AC: 112 AN: 10610

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0358 AC: 2437 AN: 68000

Other (OTH) AF: 0.0698 AC: 147 AN: 2106

Alfa AF: 0.0443 Hom.: 50

Bravo AF: 0.0665

TwinsUK AF: 0.0324 AC: 120

ALSPAC AF: 0.0304 AC: 117

ESP6500AA AF: 0.0924 AC: 279

ESP6500EA AF: 0.0380 AC: 206

ExAC AF: 0.0444 AC: 5368

Asia WGS AF: 0.0270 AC: 92 AN: 3478

EpiCase AF: 0.0385

EpiControl AF: 0.0411

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.90
DEOGEN2	Benign	0.019	.;T;T;T;.
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.27	T;T;.;.;T
MetaRNN	Benign	0.0025	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.6	.;H;H;.;H
PhyloP100		-0.084
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.0	D;D;D;N;D
REVEL	Benign	0.098
Sift	Uncertain	0.0010	D;D;D;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D
Polyphen		1.0	D;B;B;D;.
Vest4		0.18
MPC		0.43
ClinPred		0.078	T
GERP RS		-2.0
PromoterAI		-0.011	Neutral
Varity_R		0.24
gMVP		0.27
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41551813; hg19: chr6-29795913;