6-29828349-AC-ACC

Variant names:

• chr6-29828349-A-AC
• rs3215482
• NM_001384290.1:c.343+38dupC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001384290.1(HLA-G):​c.343+38dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,586,250 control chromosomes in the GnomAD database, including 192,606 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.50 (19189 hom., cov: 0)
  • Exomes 𝑓: 0.48 (173417 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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:22927): (HLA complex group 4 pseudogene 8)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.343+38dupC		intron_variant	Intron 2 of 6	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.343+38dupC		intron_variant	Intron 2 of 6	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75558 AN: 151334 Hom.: 19157 Cov.: 0

Gnomad AFR AF: 0.545

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.511

GnomAD3 exomes AF: 0.498 AC: 111161 AN: 223212 Hom.: 29082 AF XY: 0.507 AC XY: 61131 AN XY: 120508

Gnomad AFR exome AF: 0.538

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.605

Gnomad SAS exome AF: 0.705

Gnomad FIN exome AF: 0.334

Gnomad NFE exome AF: 0.446

Gnomad OTH exome AF: 0.499

GnomAD4 exome AF: 0.484 AC: 695037 AN: 1434798 Hom.: 173417 Cov.: 49 AF XY: 0.492 AC XY: 349493 AN XY: 710584

Gnomad4 AFR exome AF: 0.550

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.573

Gnomad4 EAS exome AF: 0.660

Gnomad4 SAS exome AF: 0.710

Gnomad4 FIN exome AF: 0.344

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.520

GnomAD4 genome AF: 0.499 AC: 75636 AN: 151452 Hom.: 19189 Cov.: 0 AF XY: 0.501 AC XY: 37011 AN XY: 73940

Gnomad4 AFR AF: 0.545

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.621

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.344

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.517

Asia WGS AF: 0.714 AC: 2483 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs3215482; hg19: chr6-29796126;