Genetic Variant HLA-G:c.619+90T>C (chr6-29828908-T-C) – 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.619+90T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.482 in 1,520,056 control chromosomes in the GnomAD database, including 180,411 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 ( 18072 hom., cov: 30)

Exomes 𝑓: 0.48 ( 162339 hom. )

Consequence

HLA-G
NM_001384290.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.109

Publications

15 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=-0.89).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384290.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HLA-G	NM_001384290.1	MANE Select	c.619+90T>C	intron	N/A	NP_001371219.1	Q6DU14
HLA-G	NM_001363567.2		c.634+90T>C	intron	N/A	NP_001350496.1	Q5RJ85
HLA-G	NM_001384280.1		c.634+90T>C	intron	N/A	NP_001371209.1	Q5RJ85

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HLA-G	ENST00000360323.11	TSL:6 MANE Select	c.619+90T>C	intron	N/A	ENSP00000353472.6	P17693-1
HLA-G	ENST00000376828.6	TSL:6	c.634+90T>C	intron	N/A	ENSP00000366024.2	Q5RJ85
HLA-G	ENST00000936944.1		c.619+90T>C	intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73500

AN:

151518

Hom.:

18049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.462

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:

0.499

GnomAD4 exome

AF:

0.481

AC:

658764

AN:

1368420

Hom.:

162339

AF XY:

0.489

AC XY:

334491

AN XY:

684652

show subpopulations

African (AFR)

AF:

0.510

AC:

16197

AN:

31746

American (AMR)

AF:

0.503

AC:

21765

AN:

43294

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

14301

AN:

25070

East Asian (EAS)

AF:

0.656

AC:

25657

AN:

39114

South Asian (SAS)

AF:

0.669

AC:

55769

AN:

83320

European-Finnish (FIN)

AF:

0.346

AC:

18027

AN:

52046

Middle Eastern (MID)

AF:

0.561

AC:

3137

AN:

5596

European-Non Finnish (NFE)

AF:

0.460

AC:

474674

AN:

1031028

Other (OTH)

AF:

0.511

AC:

29237

AN:

57206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

17112

34224

51337

68449

85561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14008

28016

42024

56032

70040

<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:

0.485

AC:

73564

AN:

151636

Hom.:

18072

Cov.:

AF XY:

0.485

AC XY:

35953

AN XY:

74098

show subpopulations

African (AFR)

AF:

0.510

AC:

21051

AN:

41280

American (AMR)

AF:

0.514

AC:

7845

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.567

AC:

1964

AN:

3462

East Asian (EAS)

AF:

0.611

AC:

3127

AN:

5118

South Asian (SAS)

AF:

0.667

AC:

3205

AN:

4808

European-Finnish (FIN)

AF:

0.340

AC:

3589

AN:

10554

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.459

AC:

31130

AN:

67846

Other (OTH)

AF:

0.505

AC:

1063

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1899

3797

5696

7594

9493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<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:

0.467

Hom.:

11475

Bravo

AF:

0.496

Asia WGS

AF:

0.680

AC:

2367

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

8.4

(source)

DANN

Benign

0.63

PhyloP100

-0.11

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)

0.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over