dbSNP rs1632932: HLA-G:c.1013-116G>A (chr6-29830262-G-A) – 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.1013-116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 1,128,084 control chromosomes in the GnomAD database, including 123,042 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 ( 18087 hom., cov: 30)

Exomes 𝑓: 0.45 ( 104955 hom. )

Consequence

HLA-G
NM_001384290.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0860

Publications

8 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=-0.87).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.1013-116G>A		intron_variant	Intron 5 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.1013-116G>A		intron_variant	Intron 5 of 6	6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73556

AN:

151658

Hom.:

18064

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.463

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.567

Gnomad EAS

AF:

0.611

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.340

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.500

GnomAD4 exome

AF:

0.452

AC:

441633

AN:

976308

Hom.:

104955

AF XY:

0.465

AC XY:

235539

AN XY:

506514

show subpopulations

African (AFR)

AF:

0.484

AC:

11432

AN:

23620

American (AMR)

AF:

0.502

AC:

21919

AN:

43664

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

12845

AN:

22760

East Asian (EAS)

AF:

0.654

AC:

24378

AN:

37262

South Asian (SAS)

AF:

0.663

AC:

50057

AN:

75470

European-Finnish (FIN)

AF:

0.346

AC:

18338

AN:

52984

Middle Eastern (MID)

AF:

0.548

AC:

2631

AN:

4798

European-Non Finnish (NFE)

AF:

0.415

AC:

278622

AN:

671658

Other (OTH)

AF:

0.486

AC:

21411

AN:

44092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

11030

22060

33091

44121

55151

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.485

AC:

73620

AN:

151776

Hom.:

18087

Cov.:

AF XY:

0.485

AC XY:

35960

AN XY:

74148

show subpopulations

African (AFR)

AF:

0.510

AC:

21082

AN:

41354

American (AMR)

AF:

0.514

AC:

7846

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.567

AC:

1969

AN:

3470

East Asian (EAS)

AF:

0.611

AC:

3148

AN:

5156

South Asian (SAS)

AF:

0.666

AC:

3193

AN:

4794

European-Finnish (FIN)

AF:

0.340

AC:

3592

AN:

10556

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.459

AC:

31132

AN:

67880

Other (OTH)

AF:

0.506

AC:

1065

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1861

3721

5582

7442

9303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.472

Hom.:

2198

Bravo

AF:

0.496

Asia WGS

AF:

0.685

AC:

2382

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

-0.086

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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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rs1632932

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