rs41557518

chr6-29828657-AC-Achr6-29828657-AC-ACC

Variant summary

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

The NM_001384290.1(HLA-G):c.460del(p.Leu154CysfsTer60) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,460 control chromosomes in the GnomAD database, including 347 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.028 (101 hom., cov: 32)
  • Exomes 𝑓: 0.013 (246 hom.)
• Consequence: HLA-G NM_001384290.1 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.527

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.460del	p.Leu154CysfsTer60	frameshift_variant	3/7	ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.460del	p.Leu154CysfsTer60	frameshift_variant	3/7		NM_001384290.1	P2

Frequencies

GnomAD3 genomes AF: 0.0281 AC: 4276 AN: 152178 Hom.: 101 Cov.: 32

Gnomad AFR AF: 0.0686

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0182

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.0194

Gnomad SAS AF: 0.0112

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0330

GnomAD3 exomes AF: 0.0167 AC: 4149 AN: 247946 Hom.: 67 AF XY: 0.0164 AC XY: 2212 AN XY: 134810

Gnomad AFR exome AF: 0.0702

Gnomad AMR exome AF: 0.0144

Gnomad ASJ exome AF: 0.0218

Gnomad EAS exome AF: 0.0189

Gnomad SAS exome AF: 0.0141

Gnomad FIN exome AF: 0.00176

Gnomad NFE exome AF: 0.0127

Gnomad OTH exome AF: 0.0187

GnomAD4 exome AF: 0.0130 AC: 18956 AN: 1461164 Hom.: 246 Cov.: 44 AF XY: 0.0131 AC XY: 9543 AN XY: 726922

Gnomad4 AFR exome AF: 0.0741

Gnomad4 AMR exome AF: 0.0146

Gnomad4 ASJ exome AF: 0.0203

Gnomad4 EAS exome AF: 0.0115

Gnomad4 SAS exome AF: 0.0149

Gnomad4 FIN exome AF: 0.00199

Gnomad4 NFE exome AF: 0.0110

Gnomad4 OTH exome AF: 0.0175

GnomAD4 genome AF: 0.0281 AC: 4275 AN: 152296 Hom.: 101 Cov.: 32 AF XY: 0.0275 AC XY: 2045 AN XY: 74484

Gnomad4 AFR AF: 0.0685

Gnomad4 AMR AF: 0.0181

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.0195

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.0322

Alfa AF: 0.00668 Hom.: 8

Bravo AF: 0.0332

Asia WGS AF: 0.0130 AC: 46 AN: 3478

EpiCase AF: 0.0161

EpiControl AF: 0.0168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs41557518; hg19: chr6-29796434;