6-29828488-G-T

Position:

• chr6-29828488-G-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.344-55G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 1,583,274 control chromosomes in the GnomAD database, including 1,717 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 0.058 (367 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1350 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.344-55G>T		intron_variant		ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.344-55G>T		intron_variant			NM_001384290.1	ENSP00000353472	P2

Frequencies

GnomAD3 genomes AF: 0.0576 AC: 8752 AN: 152038 Hom.: 361 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.0773

Gnomad EAS AF: 0.00715

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0718

GnomAD4 exome AF: 0.0380 AC: 54324 AN: 1431118 Hom.: 1350 Cov.: 49 AF XY: 0.0377 AC XY: 26747 AN XY: 708858

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0958

Gnomad4 ASJ exome AF: 0.0774

Gnomad4 EAS exome AF: 0.00700

Gnomad4 SAS exome AF: 0.0376

Gnomad4 FIN exome AF: 0.0126

Gnomad4 NFE exome AF: 0.0347

Gnomad4 OTH exome AF: 0.0434

GnomAD4 genome AF: 0.0577 AC: 8772 AN: 152156 Hom.: 367 Cov.: 32 AF XY: 0.0549 AC XY: 4083 AN XY: 74380

Gnomad4 AFR AF: 0.103

Gnomad4 AMR AF: 0.0858

Gnomad4 ASJ AF: 0.0773

Gnomad4 EAS AF: 0.00717

Gnomad4 SAS AF: 0.0291

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.0360

Gnomad4 OTH AF: 0.0711

Alfa AF: 0.0435 Hom.: 20

Bravo AF: 0.0669

Asia WGS AF: 0.0260 AC: 91 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.58

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: rs17875401; hg19: chr6-29796265;