chr6-29831026-C-G

Position:

• chr6-29831026-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000376828.6(HLA-G):​c.*287C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 181,036 control chromosomes in the GnomAD database, including 10,406 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 (6269 hom., cov: 33)
  • Exomes 𝑓: 0.52 (4137 hom.)
• Consequence: HLA-G ENST00000376828.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1			downstream_gene_variant		ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11			downstream_gene_variant			NM_001384290.1	P2

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43264 AN: 152016 Hom.: 6265 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.213

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.310

Gnomad OTH AF: 0.289

GnomAD4 exome AF: 0.518 AC: 14975 AN: 28902 Hom.: 4137 Cov.: 0 AF XY: 0.521 AC XY: 8356 AN XY: 16024

Gnomad4 AFR exome AF: 0.545

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.599

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.587

Gnomad4 NFE exome AF: 0.543

Gnomad4 OTH exome AF: 0.513

GnomAD4 genome AF: 0.285 AC: 43293 AN: 152134 Hom.: 6269 Cov.: 33 AF XY: 0.280 AC XY: 20812 AN XY: 74372

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.213

Gnomad4 NFE AF: 0.310

Gnomad4 OTH AF: 0.286

Alfa AF: 0.303 Hom.: 920

Bravo AF: 0.290

Asia WGS AF: 0.191 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.48
DANN	Benign	0.49

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

Publications

LitVar

Other links and lift over

dbSNP: rs1610696; hg19: chr6-29798803;