dbSNP rs1610696: HLA-G:n.1426C>G (chr6-29831026-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000478355.5(HLA-G):n.1426C>G 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 0.322 in 181,036 control chromosomes in the GnomAD database, including 10,406 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 ( 6269 hom., cov: 33)

Exomes 𝑓: 0.52 ( 4137 hom. )

Consequence

HLA-G
ENST00000478355.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.94

Publications

75 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:

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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=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.*287C>G		downstream_gene_variant		ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11 link	c.*287C>G		downstream_gene_variant		6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43264

AN:

152016

Hom.:

6265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.289

GnomAD4 exome

AF:

0.518

AC:

14975

AN:

28902

Hom.:

4137

Cov.:

AF XY:

0.521

AC XY:

8356

AN XY:

16024

show subpopulations

African (AFR)

AF:

0.545

AC:

363

AN:

666

American (AMR)

AF:

0.445

AC:

1193

AN:

2678

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

478

AN:

798

East Asian (EAS)

AF:

0.206

AC:

203

AN:

986

South Asian (SAS)

AF:

0.517

AC:

3314

AN:

6406

European-Finnish (FIN)

AF:

0.587

AC:

383

AN:

652

Middle Eastern (MID)

AF:

0.573

AC:

AN:

110

European-Non Finnish (NFE)

AF:

0.543

AC:

8279

AN:

15244

Other (OTH)

AF:

0.513

AC:

699

AN:

1362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.613

Heterozygous variant carriers

218

435

653

870

1088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.285

AC:

43293

AN:

152134

Hom.:

6269

Cov.:

AF XY:

0.280

AC XY:

20812

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.270

AC:

11193

AN:

41508

American (AMR)

AF:

0.289

AC:

4409

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

1388

AN:

3470

East Asian (EAS)

AF:

0.115

AC:

598

AN:

5190

South Asian (SAS)

AF:

0.297

AC:

1435

AN:

4826

European-Finnish (FIN)

AF:

0.213

AC:

2248

AN:

10562

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.310

AC:

21072

AN:

67986

Other (OTH)

AF:

0.286

AC:

603

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1647

3293

4940

6586

8233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.303

Hom.:

920

Bravo

AF:

0.290

Asia WGS

AF:

0.191

AC:

668

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.48

(source)

DANN

Benign

0.49

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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