rs17875403

Positions:

• chr6-29828860-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001384290.1(HLA-G):​c.619+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,612,828 control chromosomes in the GnomAD database, including 25 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 0.0064 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0035 (22 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370

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]

HLA-G (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.619+42C>T		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.619+42C>T		intron_variant		6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.00640 AC: 974 AN: 152112 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0136

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00374

Gnomad OTH AF: 0.00956

GnomAD3 exomes AF: 0.00400 AC: 991 AN: 247844 Hom.: 7 AF XY: 0.00393 AC XY: 529 AN XY: 134506

Gnomad AFR exome AF: 0.0138

Gnomad AMR exome AF: 0.00423

Gnomad ASJ exome AF: 0.0151

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00114

Gnomad FIN exome AF: 0.000417

Gnomad NFE exome AF: 0.00371

Gnomad OTH exome AF: 0.00395

GnomAD4 exome AF: 0.00354 AC: 5172 AN: 1460598 Hom.: 22 Cov.: 41 AF XY: 0.00351 AC XY: 2549 AN XY: 726682

Gnomad4 AFR exome AF: 0.0150

Gnomad4 AMR exome AF: 0.00519

Gnomad4 ASJ exome AF: 0.0152

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00118

Gnomad4 FIN exome AF: 0.000338

Gnomad4 NFE exome AF: 0.00323

Gnomad4 OTH exome AF: 0.00479

GnomAD4 genome AF: 0.00644 AC: 981 AN: 152230 Hom.: 3 Cov.: 32 AF XY: 0.00629 AC XY: 468 AN XY: 74404

Gnomad4 AFR AF: 0.0137

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00374

Gnomad4 OTH AF: 0.00946

Alfa AF: 0.00710 Hom.: 1

Bravo AF: 0.00732

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.4
DANN	Benign	0.67

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: rs17875403; hg19: chr6-29796637;