6-29828329-G-T

Position:

• chr6-29828329-G-T

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+13G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0402 in 1,597,234 control chromosomes in the GnomAD database, including 1,741 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 0.062 (374 hom., cov: 33)
  • Exomes 𝑓: 0.038 (1367 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00100

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.343+13G>T		intron_variant		ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.343+13G>T		intron_variant			NM_001384290.1	P2
HCG4P8	ENST00000443049.1	n.36C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0617 AC: 8859 AN: 143566 Hom.: 369 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.00114

Gnomad AMR AF: 0.0913

Gnomad ASJ AF: 0.0801

Gnomad EAS AF: 0.00834

Gnomad SAS AF: 0.0343

Gnomad FIN AF: 0.0109

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0780

GnomAD3 exomes AF: 0.0464 AC: 11105 AN: 239304 Hom.: 383 AF XY: 0.0436 AC XY: 5663 AN XY: 129826

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0935

Gnomad ASJ exome AF: 0.0785

Gnomad EAS exome AF: 0.00385

Gnomad SAS exome AF: 0.0392

Gnomad FIN exome AF: 0.0118

Gnomad NFE exome AF: 0.0357

Gnomad OTH exome AF: 0.0503

GnomAD4 exome AF: 0.0381 AC: 55313 AN: 1453550 Hom.: 1367 Cov.: 55 AF XY: 0.0378 AC XY: 27274 AN XY: 722210

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.0941

Gnomad4 ASJ exome AF: 0.0775

Gnomad4 EAS exome AF: 0.00705

Gnomad4 SAS exome AF: 0.0377

Gnomad4 FIN exome AF: 0.0127

Gnomad4 NFE exome AF: 0.0346

Gnomad4 OTH exome AF: 0.0436

GnomAD4 genome AF: 0.0618 AC: 8878 AN: 143684 Hom.: 374 Cov.: 33 AF XY: 0.0591 AC XY: 4140 AN XY: 70054

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0919

Gnomad4 ASJ AF: 0.0801

Gnomad4 EAS AF: 0.00836

Gnomad4 SAS AF: 0.0348

Gnomad4 FIN AF: 0.0109

Gnomad4 NFE AF: 0.0372

Gnomad4 OTH AF: 0.0771

Alfa AF: 0.0221 Hom.: 18

Bravo AF: 0.0676

Asia WGS AF: 0.0270 AC: 93 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.9
DANN	Benign	0.71

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: rs17875399; hg19: chr6-29796106;