rs1233331

Positions:

• chr6-29831057-G-A
• chr6-29831057-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000376828.6(HLA-G):​c.*318G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 186,030 control chromosomes in the GnomAD database, including 56 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 0.025 (54 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (2 hom.)
• Consequence: HLA-G ENST00000376828.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646

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=-0.92).
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0254 (3869/152340) while in subpopulation AMR AF= 0.0422 (646/15302). AF 95% confidence interval is 0.0395. There are 54 homozygotes in gnomad4. There are 1803 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 54 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1	c.*318G>A		downstream_gene_variant		ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11	c.*318G>A		downstream_gene_variant		6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3853 AN: 152222 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0226

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0302

Gnomad OTH AF: 0.0392

GnomAD4 exome AF: 0.00606 AC: 204 AN: 33690 Hom.: 2 Cov.: 0 AF XY: 0.00536 AC XY: 100 AN XY: 18642

Gnomad4 AFR exome AF: 0.00654

Gnomad4 AMR exome AF: 0.0144

Gnomad4 ASJ exome AF: 0.00106

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00812

Gnomad4 OTH exome AF: 0.00432

GnomAD4 genome AF: 0.0254 AC: 3869 AN: 152340 Hom.: 54 Cov.: 32 AF XY: 0.0242 AC XY: 1803 AN XY: 74494

Gnomad4 AFR AF: 0.0229

Gnomad4 AMR AF: 0.0422

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.0302

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0240 Hom.: 2

Bravo AF: 0.0296

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.5
DANN	Benign	0.28

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: rs1233331; hg19: chr6-29798834;