6-29828863-T-C

Position:

• chr6-29828863-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.619+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,605,552 control chromosomes in the GnomAD database, including 225,030 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 0.55 (22833 hom., cov: 30)
  • Exomes 𝑓: 0.52 (202197 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.619+45T>C		intron_variant		ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.619+45T>C		intron_variant			NM_001384290.1	P2

Frequencies

GnomAD3 genomes AF: 0.547 AC: 82404 AN: 150738 Hom.: 22799 Cov.: 30

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.691

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.578

GnomAD3 exomes AF: 0.544 AC: 134474 AN: 247242 Hom.: 38073 AF XY: 0.550 AC XY: 73823 AN XY: 134148

Gnomad AFR exome AF: 0.618

Gnomad AMR exome AF: 0.594

Gnomad ASJ exome AF: 0.651

Gnomad EAS exome AF: 0.603

Gnomad SAS exome AF: 0.713

Gnomad FIN exome AF: 0.349

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.547

GnomAD4 exome AF: 0.522 AC: 759111 AN: 1454694 Hom.: 202197 Cov.: 37 AF XY: 0.528 AC XY: 382554 AN XY: 723926

Gnomad4 AFR exome AF: 0.616

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.652

Gnomad4 EAS exome AF: 0.663

Gnomad4 SAS exome AF: 0.710

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.498

Gnomad4 OTH exome AF: 0.557

GnomAD4 genome AF: 0.547 AC: 82488 AN: 150858 Hom.: 22833 Cov.: 30 AF XY: 0.544 AC XY: 40106 AN XY: 73704

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.603

Gnomad4 ASJ AF: 0.647

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.355

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.583

Alfa AF: 0.517 Hom.: 18513

Bravo AF: 0.563

Asia WGS AF: 0.712 AC: 2475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.0
DANN	Benign	0.23

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: rs1632942; hg19: chr6-29796640; COSMIC: COSV64405850; COSMIC: COSV64405850;