rs6932888

Positions:

• chr6-29827970-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.73+53G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,586,400 control chromosomes in the GnomAD database, including 73,869 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 0.27 (5889 hom., cov: 31)
  • Exomes 𝑓: 0.30 (67980 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.171

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]

HCG4P8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.73+53G>C		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.73+53G>C		intron_variant		6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.271 AC: 40998 AN: 151496 Hom.: 5886 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.358

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.172

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.166

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.247

GnomAD4 exome AF: 0.303 AC: 434545 AN: 1434788 Hom.: 67980 Cov.: 48 AF XY: 0.299 AC XY: 212510 AN XY: 711400

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.294

Gnomad4 ASJ exome AF: 0.218

Gnomad4 EAS exome AF: 0.320

Gnomad4 SAS exome AF: 0.167

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.318

Gnomad4 OTH exome AF: 0.274

GnomAD4 genome AF: 0.270 AC: 41006 AN: 151612 Hom.: 5889 Cov.: 31 AF XY: 0.270 AC XY: 19964 AN XY: 74016

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.322

Gnomad4 OTH AF: 0.244

Alfa AF: 0.296 Hom.: 787

Bravo AF: 0.260

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.6
DANN	Benign	0.37

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: rs6932888; hg19: chr6-29795747;