dbSNP rs1130356: HLA-G:p.His117His (chr6-29828550-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001384290.1(HLA-G):c.351C>T(p.His117His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,612,148 control chromosomes in the GnomAD database, including 80,020 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 0.28 ( 6277 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73743 hom. )

Consequence

HLA-G
NM_001384290.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.322

Publications

20 publications found

Variant links:

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 links:

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

HCG4P8 links:

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

HLA-F-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.351C>T	p.His117His	synonymous_variant	Exon 3 of 7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11 link	c.351C>T	p.His117His	synonymous_variant	Exon 3 of 7	6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43228

AN:

151900

Hom.:

6273

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.258

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.296

Gnomad FIN

AF:

0.212

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.288

GnomAD2 exomes

AF:

0.284

AC:

70029

AN:

246148

AF XY:

0.290

show subpopulations

Gnomad AFR exome

AF:

0.265

Gnomad AMR exome

AF:

0.283

Gnomad ASJ exome

AF:

0.404

Gnomad EAS exome

AF:

0.0929

Gnomad FIN exome

AF:

0.211

Gnomad NFE exome

AF:

0.308

Gnomad OTH exome

AF:

0.295

GnomAD4 exome

AF:

0.314

AC:

457897

AN:

1460130

Hom.:

73743

Cov.:

AF XY:

0.316

AC XY:

229315

AN XY:

726326

show subpopulations

African (AFR)

AF:

0.268

AC:

8963

AN:

33468

American (AMR)

AF:

0.286

AC:

12767

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.403

AC:

10513

AN:

26096

East Asian (EAS)

AF:

0.154

AC:

6115

AN:

39692

South Asian (SAS)

AF:

0.337

AC:

29054

AN:

86244

European-Finnish (FIN)

AF:

0.218

AC:

11406

AN:

52236

Middle Eastern (MID)

AF:

0.346

AC:

1993

AN:

5768

European-Non Finnish (NFE)

AF:

0.322

AC:

358149

AN:

1111556

Other (OTH)

AF:

0.314

AC:

18937

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

16583

33165

49748

66330

82913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.285

AC:

43257

AN:

152018

Hom.:

6277

Cov.:

AF XY:

0.280

AC XY:

20772

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.269

AC:

11158

AN:

41460

American (AMR)

AF:

0.289

AC:

4409

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

1385

AN:

3466

East Asian (EAS)

AF:

0.113

AC:

579

AN:

5140

South Asian (SAS)

AF:

0.296

AC:

1429

AN:

4820

European-Finnish (FIN)

AF:

0.212

AC:

2251

AN:

10596

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.311

AC:

21102

AN:

67942

Other (OTH)

AF:

0.284

AC:

599

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1582

3163

4745

6326

7908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.303

Hom.:

4835

Bravo

AF:

0.290

Asia WGS

AF:

0.191

AC:

668

AN:

3478

EpiCase

AF:

0.331

EpiControl

AF:

0.318

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.32

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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rs1130356

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over