rs2735022

chr6-29827156-A-Gchr6-29827156-A-T

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+112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.498 in 466,350 control chromosomes in the GnomAD database, including 59,998 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 (18128 hom., cov: 32)
  • Exomes 𝑓: 0.50 (41870 hom.)
• Consequence: HLA-G NM_001363567.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-G	NM_001363567.2	c.6+112A>G		intron_variant
HLA-G	NM_001384280.1	c.6+112A>G		intron_variant
HLA-G	NM_002127.6	c.-113+112A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-G	ENST00000376828.6	c.6+112A>G		intron_variant				A2
HLA-G	ENST00000428701.6	n.66+112A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73688 AN: 151908 Hom.: 18105 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.500

GnomAD4 exome AF: 0.504 AC: 158567 AN: 314324 Hom.: 41870 AF XY: 0.524 AC XY: 93056 AN XY: 177582

Gnomad4 AFR exome AF: 0.515

Gnomad4 AMR exome AF: 0.504

Gnomad4 ASJ exome AF: 0.572

Gnomad4 EAS exome AF: 0.607

Gnomad4 SAS exome AF: 0.670

Gnomad4 FIN exome AF: 0.342

Gnomad4 NFE exome AF: 0.457

Gnomad4 OTH exome AF: 0.501

GnomAD4 genome AF: 0.485 AC: 73752 AN: 152026 Hom.: 18128 Cov.: 32 AF XY: 0.485 AC XY: 36042 AN XY: 74294

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.514

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.611

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.506

Alfa AF: 0.406 Hom.: 2340

Bravo AF: 0.496

Asia WGS AF: 0.685 AC: 2383 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	2.6
Dann	Benign	0.48

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: rs2735022; hg19: chr6-29794933;