rs1736927

Positions:

• chr6-29828338-A-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.343+22A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 1,595,332 control chromosomes in the GnomAD database, including 228,475 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 0.56 (24088 hom., cov: 32)
  • Exomes 𝑓: 0.53 (204387 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.343+22A>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.343+22A>C		intron_variant		6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84376 AN: 151608 Hom.: 24045 Cov.: 32

Gnomad AFR AF: 0.649

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.753

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.582

GnomAD3 exomes AF: 0.550 AC: 130346 AN: 237076 Hom.: 37425 AF XY: 0.557 AC XY: 71690 AN XY: 128700

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.594

Gnomad ASJ exome AF: 0.654

Gnomad EAS exome AF: 0.611

Gnomad SAS exome AF: 0.747

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.487

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.526 AC: 759085 AN: 1443606 Hom.: 204387 Cov.: 52 AF XY: 0.534 AC XY: 382476 AN XY: 716752

Gnomad4 AFR exome AF: 0.656

Gnomad4 AMR exome AF: 0.602

Gnomad4 ASJ exome AF: 0.654

Gnomad4 EAS exome AF: 0.671

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.498

Gnomad4 OTH exome AF: 0.566

GnomAD4 genome AF: 0.557 AC: 84473 AN: 151726 Hom.: 24088 Cov.: 32 AF XY: 0.555 AC XY: 41137 AN XY: 74130

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.608

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.754

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.587

Alfa AF: 0.531 Hom.: 5022

Bravo AF: 0.579

Asia WGS AF: 0.741 AC: 2576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.9
DANN	Benign	0.29

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: rs1736927; hg19: chr6-29796115; COSMIC: COSV64405591;