dbSNP rs1049033: HLA-G:p.Gly314Gly (chr6-29829862-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001384290.1(HLA-G):c.942C>T(p.Gly314Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,612,362 control chromosomes in the GnomAD database, including 69,845 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 0.27 ( 5526 hom., cov: 31)

Exomes 𝑓: 0.29 ( 64319 hom. )

Consequence

HLA-G
NM_001384290.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58

Publications

22 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.942C>T	p.Gly314Gly	synonymous_variant	Exon 5 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.942C>T	p.Gly314Gly	synonymous_variant	Exon 5 of 7	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40607

AN:

151902

Hom.:

5524

Cov.:

show subpopulations

Gnomad AFR

AF:

0.257

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.276

Gnomad ASJ

AF:

0.382

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.273

GnomAD2 exomes

AF:

0.266

AC:

66809

AN:

251054

AF XY:

0.270

show subpopulations

Gnomad AFR exome

AF:

0.255

Gnomad AMR exome

AF:

0.271

Gnomad ASJ exome

AF:

0.386

Gnomad EAS exome

AF:

0.0873

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.288

Gnomad OTH exome

AF:

0.273

GnomAD4 exome

AF:

0.292

AC:

426842

AN:

1460342

Hom.:

64319

Cov.:

AF XY:

0.294

AC XY:

213427

AN XY:

726584

show subpopulations

African (AFR)

AF:

0.256

AC:

8553

AN:

33450

American (AMR)

AF:

0.274

AC:

12220

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

10013

AN:

26108

East Asian (EAS)

AF:

0.151

AC:

5997

AN:

39690

South Asian (SAS)

AF:

0.303

AC:

26089

AN:

86202

European-Finnish (FIN)

AF:

0.203

AC:

10851

AN:

53412

Middle Eastern (MID)

AF:

0.304

AC:

1754

AN:

5762

European-Non Finnish (NFE)

AF:

0.300

AC:

333734

AN:

1110702

Other (OTH)

AF:

0.292

AC:

17631

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

15579

31158

46736

62315

77894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10998

21996

32994

43992

54990

<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:

0.267

AC:

40630

AN:

152020

Hom.:

5526

Cov.:

AF XY:

0.263

AC XY:

19547

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.257

AC:

10651

AN:

41428

American (AMR)

AF:

0.276

AC:

4215

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.382

AC:

1327

AN:

3470

East Asian (EAS)

AF:

0.109

AC:

561

AN:

5162

South Asian (SAS)

AF:

0.265

AC:

1279

AN:

4818

European-Finnish (FIN)

AF:

0.193

AC:

2040

AN:

10582

Middle Eastern (MID)

AF:

0.354

AC:

104

AN:

294

European-Non Finnish (NFE)

AF:

0.290

AC:

19705

AN:

67972

Other (OTH)

AF:

0.269

AC:

567

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1486

2972

4459

5945

7431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

434

868

1302

1736

2170

<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:

0.289

Hom.:

3933

Bravo

AF:

0.273

Asia WGS

AF:

0.178

AC:

625

AN:

3478

EpiCase

AF:

0.308

EpiControl

AF:

0.294

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.54

PhyloP100

-1.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.26

Position offset: 17

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