rs17179101

Positions:

• chr6-29830857-C-A

Variant summary

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

The NM_001384290.1(HLA-G):​c.*118C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0778 in 411,320 control chromosomes in the GnomAD database, including 2,753 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 0.052 (379 hom., cov: 32)
  • Exomes 𝑓: 0.093 (2374 hom.)
• Consequence: HLA-G NM_001384290.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.*118C>A		3_prime_UTR_variant	7/7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.*118C>A		3_prime_UTR_variant	7/7		NM_001384290.1	ENSP00000353472	P2

Frequencies

GnomAD3 genomes AF: 0.0522 AC: 7935 AN: 152090 Hom.: 375 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0446

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0608

Gnomad OTH AF: 0.0527

GnomAD4 exome AF: 0.0928 AC: 24048 AN: 259112 Hom.: 2374 Cov.: 0 AF XY: 0.102 AC XY: 15120 AN XY: 147942

Gnomad4 AFR exome AF: 0.0130

Gnomad4 AMR exome AF: 0.0476

Gnomad4 ASJ exome AF: 0.0687

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.179

Gnomad4 FIN exome AF: 0.0542

Gnomad4 NFE exome AF: 0.0698

Gnomad4 OTH exome AF: 0.0814

GnomAD4 genome AF: 0.0522 AC: 7941 AN: 152208 Hom.: 379 Cov.: 32 AF XY: 0.0545 AC XY: 4056 AN XY: 74424

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.0446

Gnomad4 ASJ AF: 0.0568

Gnomad4 EAS AF: 0.190

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.0391

Gnomad4 NFE AF: 0.0608

Gnomad4 OTH AF: 0.0555

Alfa AF: 0.0517 Hom.: 27

Bravo AF: 0.0486

Asia WGS AF: 0.162 AC: 562 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.24

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: rs17179101; hg19: chr6-29798634; COSMIC: COSV64405703; COSMIC: COSV64405703;