chr6-29830005-T-C

Position:

• chr6-29830005-T-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.1012+73T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,079,498 control chromosomes in the GnomAD database, including 90,737 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 0.43 (14491 hom., cov: 31)
  • Exomes 𝑓: 0.40 (76246 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.1012+73T>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.1012+73T>C		intron_variant			NM_001384290.1	ENSP00000353472	P2

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65658 AN: 151784 Hom.: 14467 Cov.: 31

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.363

Gnomad AMR AF: 0.470

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.446

GnomAD4 exome AF: 0.398 AC: 369057 AN: 927596 Hom.: 76246 AF XY: 0.404 AC XY: 192928 AN XY: 476986

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.462

Gnomad4 ASJ exome AF: 0.504

Gnomad4 EAS exome AF: 0.550

Gnomad4 SAS exome AF: 0.511

Gnomad4 FIN exome AF: 0.307

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.421

GnomAD4 genome AF: 0.433 AC: 65716 AN: 151902 Hom.: 14491 Cov.: 31 AF XY: 0.430 AC XY: 31941 AN XY: 74264

Gnomad4 AFR AF: 0.498

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.416

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.449

Alfa AF: 0.418 Hom.: 1665

Bravo AF: 0.447

Asia WGS AF: 0.515 AC: 1793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	13
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: rs1611627; hg19: chr6-29797782; COSMIC: COSV64407049; COSMIC: COSV64407049;