6-29829776-G-C

Position:

• chr6-29829776-G-C

Variant summary

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

The NM_001384290.1(HLA-G):​c.896-40G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.481 in 1,601,304 control chromosomes in the GnomAD database, including 190,314 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 (18100 hom., cov: 30)
  • Exomes 𝑓: 0.48 (172214 hom.)
• Consequence: HLA-G NM_001384290.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.478

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]

HLA-G (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• 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	Protein	UniProt
HLA-G	NM_001384290.1	c.896-40G>C		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.896-40G>C		intron_variant		6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73589 AN: 151670 Hom.: 18077 Cov.: 30

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.567

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: 0.499

GnomAD3 exomes AF: 0.497 AC: 122249 AN: 246156 Hom.: 31763 AF XY: 0.506 AC XY: 67271 AN XY: 133044

Gnomad AFR exome AF: 0.514

Gnomad AMR exome AF: 0.498

Gnomad ASJ exome AF: 0.572

Gnomad EAS exome AF: 0.599

Gnomad SAS exome AF: 0.674

Gnomad FIN exome AF: 0.336

Gnomad NFE exome AF: 0.454

Gnomad OTH exome AF: 0.494

GnomAD4 exome AF: 0.481 AC: 697273 AN: 1449516 Hom.: 172214 Cov.: 30 AF XY: 0.488 AC XY: 352085 AN XY: 721368

Gnomad4 AFR exome AF: 0.511

Gnomad4 AMR exome AF: 0.503

Gnomad4 ASJ exome AF: 0.572

Gnomad4 EAS exome AF: 0.655

Gnomad4 SAS exome AF: 0.671

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.511

GnomAD4 genome AF: 0.485 AC: 73653 AN: 151788 Hom.: 18100 Cov.: 30 AF XY: 0.485 AC XY: 36004 AN XY: 74204

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.667

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.505

Alfa AF: 0.478 Hom.: 3191

Bravo AF: 0.496

Asia WGS AF: 0.685 AC: 2382 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.9
DANN	Benign	0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1632937; hg19: chr6-29797553; COSMIC: COSV64405374; COSMIC: COSV64405374;