rs17875397

Variant names:

• chr6-29827789-C-T
• rs17875397
• ENST00000428701.6:n.123C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000428701.6(HLA-G):​n.123C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,551,432 control chromosomes in the GnomAD database, including 1,742 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 (370 hom., cov: 32)
  • Exomes 𝑓: 0.039 (1372 hom.)
• Consequence: HLA-G ENST00000428701.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857
• Publications: 14 publications found

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)

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428701.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	NM_002127.6		c.-56C>T		5_prime_UTR	Exon 2 of 8	NP_002118.1
	HLA-G	NM_001363567.2		c.7-47C>T		intron	N/A	NP_001350496.1
	HLA-G	NM_001384280.1		c.7-47C>T		intron	N/A	NP_001371209.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-G	ENST00000428701.6	TSL:6	n.123C>T		non_coding_transcript_exon	Exon 2 of 5
	HCG4P8	ENST00000443049.1	TSL:6	n.576G>A		non_coding_transcript_exon	Exon 1 of 1
	HLA-F-AS1	ENST00000849935.1		n.161G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8770 AN: 152114 Hom.: 364 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0852

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.00752

Gnomad SAS AF: 0.0286

Gnomad FIN AF: 0.0104

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0725

GnomAD2 exomes AF: 0.0455 AC: 11247 AN: 247148 AF XY: 0.0428

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0936

Gnomad ASJ exome AF: 0.0757

Gnomad EAS exome AF: 0.00388

Gnomad FIN exome AF: 0.0117

Gnomad NFE exome AF: 0.0353

Gnomad OTH exome AF: 0.0496

GnomAD4 exome AF: 0.0386 AC: 54079 AN: 1399200 Hom.: 1372 Cov.: 25 AF XY: 0.0383 AC XY: 26795 AN XY: 699932

African (AFR) AF: 0.106 AC: 3380 AN: 32030

American (AMR) AF: 0.0944 AC: 4207 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.0777 AC: 1994 AN: 25672

East Asian (EAS) AF: 0.00710 AC: 279 AN: 39270

South Asian (SAS) AF: 0.0380 AC: 3213 AN: 84446

European-Finnish (FIN) AF: 0.0126 AC: 665 AN: 52608

Middle Eastern (MID) AF: 0.0879 AC: 495 AN: 5634

European-Non Finnish (NFE) AF: 0.0353 AC: 37295 AN: 1056864

Other (OTH) AF: 0.0439 AC: 2551 AN: 58130

GnomAD4 genome AF: 0.0577 AC: 8790 AN: 152232 Hom.: 370 Cov.: 32 AF XY: 0.0550 AC XY: 4096 AN XY: 74430

African (AFR) AF: 0.103 AC: 4290 AN: 41522

American (AMR) AF: 0.0857 AC: 1312 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0772 AC: 268 AN: 3470

East Asian (EAS) AF: 0.00754 AC: 39 AN: 5172

South Asian (SAS) AF: 0.0291 AC: 140 AN: 4818

European-Finnish (FIN) AF: 0.0104 AC: 110 AN: 10614

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0360 AC: 2451 AN: 68022

Other (OTH) AF: 0.0717 AC: 151 AN: 2106

Alfa AF: 0.0372 Hom.: 49

Bravo AF: 0.0670

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.3
DANN	Benign	0.91
PhyloP100		-0.86
PromoterAI		0.081	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17875397; hg19: chr6-29795566;