rs17875405

chr6-29829378-G-C

Variant summary

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

The NM_001384290.1(HLA-G):c.620-40G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 1,599,266 control chromosomes in the GnomAD database, including 1,732 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 (374 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1358 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.840

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=-0.99).
• 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	UniProt
HLA-G	NM_001384290.1	c.620-40G>C		intron_variant		ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.620-40G>C		intron_variant			NM_001384290.1	P2

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8780 AN: 152082 Hom.: 368 Cov.: 31

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.00733

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0361

Gnomad OTH AF: 0.0723

GnomAD3 exomes AF: 0.0454 AC: 10995 AN: 242330 Hom.: 389 AF XY: 0.0425 AC XY: 5556 AN XY: 130710

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.0934

Gnomad ASJ exome AF: 0.0743

Gnomad EAS exome AF: 0.00386

Gnomad SAS exome AF: 0.0368

Gnomad FIN exome AF: 0.0119

Gnomad NFE exome AF: 0.0350

Gnomad OTH exome AF: 0.0487

GnomAD4 exome AF: 0.0376 AC: 54423 AN: 1447066 Hom.: 1358 Cov.: 30 AF XY: 0.0374 AC XY: 26869 AN XY: 719010

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0941

Gnomad4 ASJ exome AF: 0.0766

Gnomad4 EAS exome AF: 0.00705

Gnomad4 SAS exome AF: 0.0373

Gnomad4 FIN exome AF: 0.0126

Gnomad4 NFE exome AF: 0.0343

Gnomad4 OTH exome AF: 0.0431

GnomAD4 genome AF: 0.0578 AC: 8800 AN: 152200 Hom.: 374 Cov.: 31 AF XY: 0.0551 AC XY: 4102 AN XY: 74412

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0858

Gnomad4 ASJ AF: 0.0773

Gnomad4 EAS AF: 0.00735

Gnomad4 SAS AF: 0.0288

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0361

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0467 Hom.: 36

Bravo AF: 0.0670

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	-0.99
Cadd	Benign	4.3
Dann	Benign	0.53

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: rs17875405; hg19: chr6-29797155;