Genetic Variant HLA-G:c.343+38dupC (chr6-29828349-A-AC) – 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.343+38dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 1,586,250 control chromosomes in the GnomAD database, including 192,606 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.50 ( 19189 hom., cov: 0)

Exomes 𝑓: 0.48 ( 173417 hom. )

Consequence

HLA-G
NM_001384290.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.482

Publications

7 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.707 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.343+38dupC		intron_variant	Intron 2 of 6	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11 link	c.343+38dupC		intron_variant	Intron 2 of 6	6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.499

AC:

75558

AN:

151334

Hom.:

19157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.545

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.523

Gnomad ASJ

AF:

0.570

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.726

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.595

Gnomad NFE

AF:

0.461

Gnomad OTH

AF:

0.511

GnomAD2 exomes

AF:

0.498

AC:

111161

AN:

223212

AF XY:

0.507

show subpopulations

Gnomad AFR exome

AF:

0.538

Gnomad AMR exome

AF:

0.498

Gnomad ASJ exome

AF:

0.569

Gnomad EAS exome

AF:

0.605

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.446

Gnomad OTH exome

AF:

0.499

GnomAD4 exome

AF:

0.484

AC:

695037

AN:

1434798

Hom.:

173417

Cov.:

AF XY:

0.492

AC XY:

349493

AN XY:

710584

show subpopulations

African (AFR)

AF:

0.550

AC:

18190

AN:

33082

American (AMR)

AF:

0.503

AC:

21835

AN:

43408

Ashkenazi Jewish (ASJ)

AF:

0.573

AC:

13934

AN:

24314

East Asian (EAS)

AF:

0.660

AC:

25963

AN:

39310

South Asian (SAS)

AF:

0.710

AC:

58103

AN:

81856

European-Finnish (FIN)

AF:

0.344

AC:

17626

AN:

51248

Middle Eastern (MID)

AF:

0.568

AC:

3206

AN:

5640

European-Non Finnish (NFE)

AF:

0.461

AC:

505381

AN:

1096700

Other (OTH)

AF:

0.520

AC:

30799

AN:

59240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

Heterozygous variant carriers

18887

37774

56662

75549

94436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.499

AC:

75636

AN:

151452

Hom.:

19189

Cov.:

AF XY:

0.501

AC XY:

37011

AN XY:

73940

show subpopulations

African (AFR)

AF:

0.545

AC:

22544

AN:

41332

American (AMR)

AF:

0.523

AC:

7981

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.570

AC:

1977

AN:

3470

East Asian (EAS)

AF:

0.621

AC:

3157

AN:

5080

South Asian (SAS)

AF:

0.727

AC:

3494

AN:

4808

European-Finnish (FIN)

AF:

0.344

AC:

3601

AN:

10466

Middle Eastern (MID)

AF:

0.588

AC:

173

AN:

294

European-Non Finnish (NFE)

AF:

0.461

AC:

31200

AN:

67734

Other (OTH)

AF:

0.517

AC:

1088

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1928

3856

5784

7712

9640

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.396

Hom.:

1693

Asia WGS

AF:

0.714

AC:

2483

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.48

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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6-29828349-AC-ACC

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