chr6-29830804-G-GATTTGTTCATGCCT

Position:

• chr6-29830804-G-GATTTGTTCATGCCT

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP5 BA1

The NM_001384290.1(HLA-G):​c.*65_*66insATTTGTTCATGCCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely risk allele (no stars).

• Frequency:
  • Genomes: 𝑓 0.40 (12057 hom., cov: 0)
  • Exomes 𝑓: 0.44 (30938 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-G NM_001384290.1 3_prime_UTR
• Clinical Significance: Likely risk allele no assertion criteria provided P:1
• Conservation: PhyloP100: -2.13

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PP5: Variant 6-29830804-G-GATTTGTTCATGCCT is Pathogenic according to our data. Variant chr6-29830804-G-GATTTGTTCATGCCT is described in ClinVar as [Likely_risk_allele]. Clinvar id is 2628037.Status of the report is no_assertion_criteria_provided, 0 stars. We mark this variant Likely_pathogenic, oryginal submission is: [Likely_risk_allele].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.*65_*66insATTTGTTCATGCCT		3_prime_UTR_variant	7/7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.*65_*66insATTTGTTCATGCCT		3_prime_UTR_variant	7/7		NM_001384290.1	ENSP00000353472	P2

Frequencies

GnomAD3 genomes AF: 0.397 AC: 60210 AN: 151684 Hom.: 12039 Cov.: 0

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.314

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.420

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.436 AC: 129872 AN: 297914 Hom.: 30938 Cov.: 0 AF XY: 0.449 AC XY: 76064 AN XY: 169446

Gnomad4 AFR exome AF: 0.387

Gnomad4 AMR exome AF: 0.425

Gnomad4 ASJ exome AF: 0.580

Gnomad4 EAS exome AF: 0.284

Gnomad4 SAS exome AF: 0.562

Gnomad4 FIN exome AF: 0.278

Gnomad4 NFE exome AF: 0.421

Gnomad4 OTH exome AF: 0.425

GnomAD4 genome AF: 0.397 AC: 60273 AN: 151802 Hom.: 12057 Cov.: 0 AF XY: 0.392 AC XY: 29085 AN XY: 74188

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.314

Gnomad4 SAS AF: 0.491

Gnomad4 FIN AF: 0.262

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.419

Alfa AF: 0.189 Hom.: 293

ClinVar

Significance: Likely risk allele

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Post-COVID-19 disorder Pathogenic:1

Likely risk allele, no assertion criteria provided

research

HLA Laboratory, Instituto Nacional de Enfermedades Respiratorias Ismael Cosio Villegas

Oct 27, 2023

Association with exercise-induced desaturation in post-COVID condition -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs371194629; hg19: chr6-29798581; COSMIC: COSV105826548; COSMIC: COSV105826548;