rs17875394

Positions:

• chr6-29827402-G-A

Variant summary

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

The NM_001363567.2(HLA-G):​c.6+358G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00869 in 354,404 control chromosomes in the GnomAD database, including 118 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 0.0097 (61 hom., cov: 32)
  • Exomes 𝑓: 0.0079 (57 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

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 = 0.0849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001363567.2	c.6+358G>A		intron_variant			NP_001350496.1
HLA-G	NM_001384280.1	c.6+358G>A		intron_variant			NP_001371209.1
HLA-G	NM_002127.6	c.-112-331G>A		intron_variant			NP_002118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000376828.6	c.6+358G>A		intron_variant		6		ENSP00000366024.2
HCG4P8	ENST00000443049.1	n.963C>T		non_coding_transcript_exon_variant	1/1	6
HLA-G	ENST00000428701.6	n.67-331G>A		intron_variant		6

Frequencies

GnomAD3 genomes AF: 0.00962 AC: 1463 AN: 152158 Hom.: 60 Cov.: 32

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0541

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0915

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000779

Gnomad OTH AF: 0.00955

GnomAD4 exome AF: 0.00794 AC: 1605 AN: 202128 Hom.: 57 Cov.: 0 AF XY: 0.00745 AC XY: 832 AN XY: 111680

Gnomad4 AFR exome AF: 0.00174

Gnomad4 AMR exome AF: 0.0663

Gnomad4 ASJ exome AF: 0.00137

Gnomad4 EAS exome AF: 0.0863

Gnomad4 SAS exome AF: 0.00201

Gnomad4 FIN exome AF: 0.00231

Gnomad4 NFE exome AF: 0.000628

Gnomad4 OTH exome AF: 0.00574

GnomAD4 genome AF: 0.00967 AC: 1473 AN: 152276 Hom.: 61 Cov.: 32 AF XY: 0.0111 AC XY: 830 AN XY: 74470

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.0546

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0917

Gnomad4 SAS AF: 0.00332

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.000779

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00266 Hom.: 3

Bravo AF: 0.0130

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.5
DANN	Benign	0.80

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: rs17875394; hg19: chr6-29795179;