rs1625035

chr6-29828480-C-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.344-63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,575,594 control chromosomes in the GnomAD database, including 219,134 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 0.54 (22762 hom., cov: 30)
  • Exomes 𝑓: 0.52 (196372 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.492

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.344-63C>T		intron_variant		ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.344-63C>T		intron_variant			NM_001384290.1	P2

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82206 AN: 151482 Hom.: 22728 Cov.: 30

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.573

GnomAD4 exome AF: 0.519 AC: 738941 AN: 1423994 Hom.: 196372 Cov.: 49 AF XY: 0.525 AC XY: 370234 AN XY: 704654

Gnomad4 AFR exome AF: 0.615

Gnomad4 AMR exome AF: 0.599

Gnomad4 ASJ exome AF: 0.651

Gnomad4 EAS exome AF: 0.662

Gnomad4 SAS exome AF: 0.709

Gnomad4 FIN exome AF: 0.360

Gnomad4 NFE exome AF: 0.496

Gnomad4 OTH exome AF: 0.555

GnomAD4 genome AF: 0.543 AC: 82290 AN: 151600 Hom.: 22762 Cov.: 30 AF XY: 0.540 AC XY: 39985 AN XY: 74032

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.578

Alfa AF: 0.514 Hom.: 2502

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	-0.88
Cadd	Benign	7.3
Dann	Benign	0.93

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: rs1625035; hg19: chr6-29796257; COSMIC: COSV64405405; COSMIC: COSV64405405;