rs9258495

chr6-29828168-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_001384290.1(HLA-G):c.195G>T(p.Ala65=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,613,374 control chromosomes in the GnomAD database, including 17 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 0.0013 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (15 hom.)
• Consequence: HLA-G NM_001384290.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=1.25 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001384290.1	c.195G>T	p.Ala65=	synonymous_variant	2/7	ENST00000360323.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000360323.11	c.195G>T	p.Ala65=	synonymous_variant	2/7		NM_001384290.1	P2
HCG4P8	ENST00000443049.1	n.197C>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 196 AN: 152246 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.000850

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00250

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00172 AC: 425 AN: 247626 Hom.: 2 AF XY: 0.00203 AC XY: 274 AN XY: 134724

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00101

Gnomad ASJ exome AF: 0.00351

Gnomad EAS exome AF: 0.00257

Gnomad SAS exome AF: 0.00582

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000999

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.00121 AC: 1772 AN: 1461010 Hom.: 15 Cov.: 89 AF XY: 0.00142 AC XY: 1034 AN XY: 726856

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.00105

Gnomad4 ASJ exome AF: 0.00314

Gnomad4 EAS exome AF: 0.00161

Gnomad4 SAS exome AF: 0.00663

Gnomad4 FIN exome AF: 0.0000946

Gnomad4 NFE exome AF: 0.000772

Gnomad4 OTH exome AF: 0.00171

GnomAD4 genome AF: 0.00129 AC: 196 AN: 152364 Hom.: 2 Cov.: 33 AF XY: 0.00140 AC XY: 104 AN XY: 74500

Gnomad4 AFR AF: 0.0000962

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00251

Gnomad4 SAS AF: 0.00497

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00102 Hom.: 0

Bravo AF: 0.00151

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.00158

EpiControl AF: 0.00107

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	9.5
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: rs9258495; hg19: chr6-29795945;