rs1130356

chr6-29828550-C-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.351C>T(p.His117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,612,148 control chromosomes in the GnomAD database, including 80,020 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 0.28 (6277 hom., cov: 32)
  • Exomes 𝑓: 0.31 (73743 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.322

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.351C>T	p.His117=	synonymous_variant	3/7	ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.351C>T	p.His117=	synonymous_variant	3/7		NM_001384290.1	P2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43228 AN: 151900 Hom.: 6273 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.288

GnomAD3 exomes AF: 0.284 AC: 70029 AN: 246148 Hom.: 10721 AF XY: 0.290 AC XY: 38958 AN XY: 134220

Gnomad AFR exome AF: 0.265

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.404

Gnomad EAS exome AF: 0.0929

Gnomad SAS exome AF: 0.336

Gnomad FIN exome AF: 0.211

Gnomad NFE exome AF: 0.308

Gnomad OTH exome AF: 0.295

GnomAD4 exome AF: 0.314 AC: 457897 AN: 1460130 Hom.: 73743 Cov.: 57 AF XY: 0.316 AC XY: 229315 AN XY: 726326

Gnomad4 AFR exome AF: 0.268

Gnomad4 AMR exome AF: 0.286

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.218

Gnomad4 NFE exome AF: 0.322

Gnomad4 OTH exome AF: 0.314

GnomAD4 genome AF: 0.285 AC: 43257 AN: 152018 Hom.: 6277 Cov.: 32 AF XY: 0.280 AC XY: 20772 AN XY: 74302

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.212

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.284

Alfa AF: 0.310 Hom.: 3502

Bravo AF: 0.290

Asia WGS AF: 0.191 AC: 668 AN: 3478

EpiCase AF: 0.331

EpiControl AF: 0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	10
Dann	Benign	0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1130356; hg19: chr6-29796327; COSMIC: COSV64405769; COSMIC: COSV64405769;