dbSNP rs17875404: HLA-G:c.619+80G>T (chr6-29828898-G-T) – 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+80G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.04 in 1,577,392 control chromosomes in the GnomAD database, including 1,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: 𝑓 0.058 ( 366 hom., cov: 31)

Exomes 𝑓: 0.038 ( 1356 hom. )

Consequence

HLA-G
NM_001384290.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0460

Publications

2 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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 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+80G>T	intron	N/A	NP_001371219.1	Q6DU14
HLA-G	NM_001363567.2		c.634+80G>T	intron	N/A	NP_001350496.1	Q5RJ85
HLA-G	NM_001384280.1		c.634+80G>T	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+80G>T	intron	N/A	ENSP00000353472.6	P17693-1
HLA-G	ENST00000376828.6	TSL:6	c.634+80G>T	intron	N/A	ENSP00000366024.2	Q5RJ85
HLA-G	ENST00000936944.1		c.619+80G>T	intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes

AF:

0.0576

AC:

8750

AN:

151982

Hom.:

360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0849

Gnomad ASJ

AF:

0.0775

Gnomad EAS

AF:

0.00733

Gnomad SAS

AF:

0.0282

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0360

Gnomad OTH

AF:

0.0722

GnomAD4 exome

AF:

0.0381

AC:

54256

AN:

1425292

Hom.:

1356

AF XY:

0.0377

AC XY:

26834

AN XY:

710914

show subpopulations

African (AFR)

AF:

0.104

AC:

3415

AN:

32800

American (AMR)

AF:

0.0943

AC:

4176

AN:

44300

Ashkenazi Jewish (ASJ)

AF:

0.0772

AC:

1983

AN:

25694

East Asian (EAS)

AF:

0.00714

AC:

282

AN:

39478

South Asian (SAS)

AF:

0.0375

AC:

3201

AN:

85296

European-Finnish (FIN)

AF:

0.0127

AC:

667

AN:

52710

Middle Eastern (MID)

AF:

0.0871

AC:

497

AN:

5708

European-Non Finnish (NFE)

AF:

0.0347

AC:

37464

AN:

1080212

Other (OTH)

AF:

0.0435

AC:

2571

AN:

59094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2770

5539

8309

11078

13848

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1482

2964

4446

5928

7410

<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:

0.0577

AC:

8770

AN:

152100

Hom.:

366

Cov.:

AF XY:

0.0549

AC XY:

4084

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.103

AC:

4279

AN:

41460

American (AMR)

AF:

0.0854

AC:

1306

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0775

AC:

268

AN:

3460

East Asian (EAS)

AF:

0.00735

AC:

AN:

5170

South Asian (SAS)

AF:

0.0286

AC:

138

AN:

4818

European-Finnish (FIN)

AF:

0.0106

AC:

112

AN:

10614

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0360

AC:

2449

AN:

67976

Other (OTH)

AF:

0.0714

AC:

151

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

411

822

1234

1645

2056

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0441

Hom.:

284

Bravo

AF:

0.0669

Asia WGS

AF:

0.0270

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

(source)

DANN

Benign

0.60

PhyloP100

0.046

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)

0.010

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.

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