rs17875404

Positions:

• chr6-29828898-G-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.619+80G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.04 in 1,577,392 control chromosomes in the GnomAD database, including 1,722 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 0.058 (366 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1356 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.619+80G>T		intron_variant		ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.619+80G>T		intron_variant			NM_001384290.1	ENSP00000353472	P2

Frequencies

GnomAD3 genomes AF: 0.0576 AC: 8750 AN: 151982 Hom.: 360 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0849

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.00733

Gnomad SAS AF: 0.0282

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0722

GnomAD4 exome AF: 0.0381 AC: 54256 AN: 1425292 Hom.: 1356 AF XY: 0.0377 AC XY: 26834 AN XY: 710914

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0943

Gnomad4 ASJ exome AF: 0.0772

Gnomad4 EAS exome AF: 0.00714

Gnomad4 SAS exome AF: 0.0375

Gnomad4 FIN exome AF: 0.0127

Gnomad4 NFE exome AF: 0.0347

Gnomad4 OTH exome AF: 0.0435

GnomAD4 genome AF: 0.0577 AC: 8770 AN: 152100 Hom.: 366 Cov.: 31 AF XY: 0.0549 AC XY: 4084 AN XY: 74368

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0854

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.00735

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0360

Gnomad4 OTH AF: 0.0714

Alfa AF: 0.0515 Hom.: 34

Bravo AF: 0.0669

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	10
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs17875404; hg19: chr6-29796675;