rs17179080

Positions:

• chr6-29830256-G-A
• chr6-29830256-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.1013-122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,111,360 control chromosomes in the GnomAD database, including 316 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 0.027 (129 hom., cov: 31)
  • Exomes 𝑓: 0.012 (187 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.340

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 = 0.0649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.1013-122G>A		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.1013-122G>A		intron_variant			NM_001384290.1	ENSP00000353472	P2

Frequencies

GnomAD3 genomes AF: 0.0270 AC: 4110 AN: 152064 Hom.: 127 Cov.: 31

Gnomad AFR AF: 0.0668

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0106

Gnomad OTH AF: 0.0330

GnomAD4 exome AF: 0.0121 AC: 11602 AN: 959178 Hom.: 187 AF XY: 0.0116 AC XY: 5782 AN XY: 498440

Gnomad4 AFR exome AF: 0.0759

Gnomad4 AMR exome AF: 0.0236

Gnomad4 ASJ exome AF: 0.0147

Gnomad4 EAS exome AF: 0.00145

Gnomad4 SAS exome AF: 0.00369

Gnomad4 FIN exome AF: 0.00155

Gnomad4 NFE exome AF: 0.0109

Gnomad4 OTH exome AF: 0.0169

GnomAD4 genome AF: 0.0271 AC: 4124 AN: 152182 Hom.: 129 Cov.: 31 AF XY: 0.0263 AC XY: 1958 AN XY: 74412

Gnomad4 AFR AF: 0.0670

Gnomad4 AMR AF: 0.0307

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00436

Gnomad4 FIN AF: 0.000754

Gnomad4 NFE AF: 0.0106

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0172 Hom.: 4

Bravo AF: 0.0321

Asia WGS AF: 0.00866 AC: 30 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	12
DANN	Benign	0.83

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: rs17179080; hg19: chr6-29798033;