chr6-29827368-C-G

Position:

• chr6-29827368-C-G

Variant summary

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

The NM_001363567.2(HLA-G):​c.6+324C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.544 in 348,770 control chromosomes in the GnomAD database, including 53,144 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 (22744 hom., cov: 31)
  • Exomes 𝑓: 0.54 (30400 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• 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	Protein	UniProt
HLA-G	NM_001363567.2	c.6+324C>G		intron_variant			NP_001350496.1
HLA-G	NM_001384280.1	c.6+324C>G		intron_variant			NP_001371209.1
HLA-G	NM_002127.6	c.-113+324C>G		intron_variant			NP_002118.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000376828.6	c.6+324C>G		intron_variant				ENSP00000366024	A2
HLA-G	ENST00000428701.6	n.66+324C>G		intron_variant, non_coding_transcript_variant
HCG4P8	ENST00000443049.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82251 AN: 151512 Hom.: 22710 Cov.: 31

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.644

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.688

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.571

GnomAD4 exome AF: 0.544 AC: 107269 AN: 197140 Hom.: 30400 Cov.: 0 AF XY: 0.565 AC XY: 61350 AN XY: 108614

Gnomad4 AFR exome AF: 0.611

Gnomad4 AMR exome AF: 0.596

Gnomad4 ASJ exome AF: 0.650

Gnomad4 EAS exome AF: 0.606

Gnomad4 SAS exome AF: 0.703

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.531

GnomAD4 genome AF: 0.543 AC: 82335 AN: 151630 Hom.: 22744 Cov.: 31 AF XY: 0.540 AC XY: 40018 AN XY: 74082

Gnomad4 AFR AF: 0.613

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.644

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.349

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.575

Alfa AF: 0.347 Hom.: 774

Bravo AF: 0.564

Asia WGS AF: 0.711 AC: 2474 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.071
DANN	Benign	0.50

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: rs1736932; hg19: chr6-29795145; COSMIC: COSV64407037; COSMIC: COSV64407037;