dbSNP rs1632942: HLA-G:c.619+45T>C (chr6-29828863-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+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,605,552 control chromosomes in the GnomAD database, including 225,030 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 0.55 ( 22833 hom., cov: 30)

Exomes 𝑓: 0.52 ( 202197 hom. )

Consequence

HLA-G
NM_001384290.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.18

Publications

27 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 -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 = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.619+45T>C		intron_variant	Intron 3 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.619+45T>C		intron_variant	Intron 3 of 6	6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

82404

AN:

150738

Hom.:

22799

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.473

Gnomad AMR

AF:

0.603

Gnomad ASJ

AF:

0.647

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.698

Gnomad FIN

AF:

0.355

Gnomad MID

AF:

0.691

Gnomad NFE

AF:

0.499

Gnomad OTH

AF:

0.578

GnomAD2 exomes

AF:

0.544

AC:

134474

AN:

247242

AF XY:

0.550

show subpopulations

Gnomad AFR exome

AF:

0.618

Gnomad AMR exome

AF:

0.594

Gnomad ASJ exome

AF:

0.651

Gnomad EAS exome

AF:

0.603

Gnomad FIN exome

AF:

0.349

Gnomad NFE exome

AF:

0.490

Gnomad OTH exome

AF:

0.547

GnomAD4 exome

AF:

0.522

AC:

759111

AN:

1454694

Hom.:

202197

Cov.:

AF XY:

0.528

AC XY:

382554

AN XY:

723926

show subpopulations

African (AFR)

AF:

0.616

AC:

20587

AN:

33418

American (AMR)

AF:

0.599

AC:

26712

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.652

AC:

16990

AN:

26064

East Asian (EAS)

AF:

0.663

AC:

26287

AN:

39666

South Asian (SAS)

AF:

0.710

AC:

61166

AN:

86182

European-Finnish (FIN)

AF:

0.360

AC:

19088

AN:

53048

Middle Eastern (MID)

AF:

0.650

AC:

3745

AN:

5758

European-Non Finnish (NFE)

AF:

0.498

AC:

550979

AN:

1105728

Other (OTH)

AF:

0.557

AC:

33557

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

19995

39990

59986

79981

99976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.547

AC:

82488

AN:

150858

Hom.:

22833

Cov.:

AF XY:

0.544

AC XY:

40106

AN XY:

73704

show subpopulations

African (AFR)

AF:

0.617

AC:

25402

AN:

41196

American (AMR)

AF:

0.603

AC:

9173

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.647

AC:

2238

AN:

3458

East Asian (EAS)

AF:

0.622

AC:

3173

AN:

5098

South Asian (SAS)

AF:

0.698

AC:

3350

AN:

4796

European-Finnish (FIN)

AF:

0.355

AC:

3711

AN:

10446

Middle Eastern (MID)

AF:

0.677

AC:

199

AN:

294

European-Non Finnish (NFE)

AF:

0.499

AC:

33602

AN:

67380

Other (OTH)

AF:

0.583

AC:

1217

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1908

3816

5724

7632

9540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.523

Hom.:

62337

Bravo

AF:

0.563

Asia WGS

AF:

0.712

AC:

2475

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.0

(source)

DANN

Benign

0.23

PhyloP100

-1.2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs1632942

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