rs1630223

chr6-29827859-G-Achr6-29827859-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001384290.1(HLA-G):c.15G>A(p.Ala5=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,608,764 control chromosomes in the GnomAD database, including 191,867 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 0.48 (18029 hom., cov: 29)
  • Exomes 𝑓: 0.48 (173838 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0840

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]

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.084 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.15G>A	p.Ala5=	synonymous_variant	1/7	ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.15G>A	p.Ala5=	synonymous_variant	1/7		NM_001384290.1	P2
HCG4P8	ENST00000443049.1	n.506C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73396 AN: 151412 Hom.: 18006 Cov.: 29

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.497

GnomAD3 exomes AF: 0.498 AC: 123579 AN: 248306 Hom.: 32180 AF XY: 0.507 AC XY: 68364 AN XY: 134862

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.499

Gnomad ASJ exome AF: 0.575

Gnomad EAS exome AF: 0.599

Gnomad SAS exome AF: 0.675

Gnomad FIN exome AF: 0.337

Gnomad NFE exome AF: 0.454

Gnomad OTH exome AF: 0.497

GnomAD4 exome AF: 0.482 AC: 701856 AN: 1457234 Hom.: 173838 Cov.: 43 AF XY: 0.489 AC XY: 354368 AN XY: 725122

Gnomad4 AFR exome AF: 0.511

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.574

Gnomad4 EAS exome AF: 0.655

Gnomad4 SAS exome AF: 0.672

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.512

GnomAD4 genome AF: 0.485 AC: 73460 AN: 151530 Hom.: 18029 Cov.: 29 AF XY: 0.485 AC XY: 35880 AN XY: 74022

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.502

Alfa AF: 0.475 Hom.: 8141

Bravo AF: 0.496

Asia WGS AF: 0.685 AC: 2382 AN: 3478

EpiCase AF: 0.490

EpiControl AF: 0.477

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	9.7
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: rs1630223; hg19: chr6-29795636; COSMIC: COSV64405573;