rs41551813

chr6-29828136-A-T

Variant summary

Our verdict is Benign. Variant got -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. 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

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)

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.163A>T	p.Thr55Ser	missense_variant	2/7	ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.163A>T	p.Thr55Ser	missense_variant	2/7		NM_001384290.1	P2
HCG4P8	ENST00000443049.1	n.229T>A		non_coding_transcript_exon_variant	1/1

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

GnomAD3 exomes AF: 0.0457 AC: 11282 AN: 247074 Hom.: 397 AF XY: 0.0429 AC XY: 5764 AN XY: 134506

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 SAS exome AF: 0.0376

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

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0930

Gnomad4 ASJ exome AF: 0.0766

Gnomad4 EAS exome AF: 0.00713

Gnomad4 SAS exome AF: 0.0375

Gnomad4 FIN exome AF: 0.0126

Gnomad4 NFE exome AF: 0.0345

Gnomad4 OTH exome AF: 0.0433

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

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0826

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.00755

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0358

Gnomad4 OTH AF: 0.0698

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
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
MutationTaster	Benign	1.0	P;P;P;P;P
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
Varity_R		0.24
gMVP		0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs41551813; hg19: chr6-29795913;