rs1233333

chr6-29827644-G-Achr6-29827644-G-Cchr6-29827644-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000443049.1(HCG4P8):n.721C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 642,566 control chromosomes in the GnomAD database, including 79,533 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 0.49 (18147 hom., cov: 32)
  • Exomes 𝑓: 0.49 (61386 hom.)
• Consequence: HCG4P8 ENST00000443049.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.929

Genes affected

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

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 = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001363567.2	c.7-192G>A		intron_variant
HLA-G	NM_001384280.1	c.7-192G>A		intron_variant
HLA-G	NM_002127.6	c.-112-89G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HCG4P8	ENST00000443049.1	n.721C>T		non_coding_transcript_exon_variant	1/1
HLA-G	ENST00000376828.6	c.7-192G>A		intron_variant				A2
HLA-G	ENST00000428701.6	n.67-89G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73716 AN: 151916 Hom.: 18124 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.461

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.488 AC: 239596 AN: 490532 Hom.: 61386 Cov.: 5 AF XY: 0.501 AC XY: 132501 AN XY: 264382

Gnomad4 AFR exome AF: 0.505

Gnomad4 AMR exome AF: 0.502

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.651

Gnomad4 SAS exome AF: 0.668

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.497

GnomAD4 genome AF: 0.485 AC: 73780 AN: 152034 Hom.: 18147 Cov.: 32 AF XY: 0.485 AC XY: 36066 AN XY: 74322

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.506

Alfa AF: 0.471 Hom.: 5342

Bravo AF: 0.496

Asia WGS AF: 0.684 AC: 2381 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	2.6
Dann	Benign	0.78

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: rs1233333; hg19: chr6-29795421; COSMIC: COSV64406088; COSMIC: COSV64406088;