rs17179108

chr6-29830865-C-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.*126C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 390,066 control chromosomes in the GnomAD database, including 5,502 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 0.11 (1117 hom., cov: 32)
  • Exomes 𝑓: 0.15 (4385 hom.)
• Consequence: HLA-G NM_001384290.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.*126C>T		3_prime_UTR_variant	7/7	ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.*126C>T		3_prime_UTR_variant	7/7		NM_001384290.1	P2

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17341 AN: 152064 Hom.: 1107 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.0513

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.154 AC: 36684 AN: 237884 Hom.: 4385 Cov.: 0 AF XY: 0.162 AC XY: 21982 AN XY: 135922

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.168

Gnomad4 EAS exome AF: 0.216

Gnomad4 SAS exome AF: 0.232

Gnomad4 FIN exome AF: 0.0803

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.114 AC: 17373 AN: 152182 Hom.: 1117 Cov.: 32 AF XY: 0.114 AC XY: 8466 AN XY: 74394

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.140

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.0513

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.134

Alfa AF: 0.0993 Hom.: 228

Bravo AF: 0.120

Asia WGS AF: 0.195 AC: 675 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	3.1
Dann	Benign	0.37

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: rs17179108; hg19: chr6-29798642; COSMIC: COSV64405197; COSMIC: COSV64405197;