dbSNP rs17875401: HLA-G:c.344-55G>T (chr6-29828488-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.344-55G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0399 in 1,583,274 control chromosomes in the GnomAD database, including 1,717 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 0.058 ( 367 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1350 hom. )

Consequence

HLA-G
NM_001384290.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96

Publications

1 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:

HLA-F-AS1 (HGNC:26645): (HLA-F antisense RNA 1)

HLA-F-AS1 links:

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

HCG4P8 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.1 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.344-55G>T		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.344-55G>T		intron_variant	Intron 2 of 6	6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.0576

AC:

8752

AN:

152038

Hom.:

361

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0852

Gnomad ASJ

AF:

0.0773

Gnomad EAS

AF:

0.00715

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0106

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0360

Gnomad OTH

AF:

0.0718

GnomAD4 exome

AF:

0.0380

AC:

54324

AN:

1431118

Hom.:

1350

Cov.:

AF XY:

0.0377

AC XY:

26747

AN XY:

708858

show subpopulations

African (AFR)

AF:

0.104

AC:

3393

AN:

32590

American (AMR)

AF:

0.0958

AC:

3992

AN:

41668

Ashkenazi Jewish (ASJ)

AF:

0.0774

AC:

1843

AN:

23820

East Asian (EAS)

AF:

0.00700

AC:

276

AN:

39428

South Asian (SAS)

AF:

0.0376

AC:

3069

AN:

81650

European-Finnish (FIN)

AF:

0.0126

AC:

643

AN:

50834

Middle Eastern (MID)

AF:

0.0890

AC:

493

AN:

5538

European-Non Finnish (NFE)

AF:

0.0347

AC:

38066

AN:

1096792

Other (OTH)

AF:

0.0434

AC:

2549

AN:

58798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2935

5870

8806

11741

14676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1534

3068

4602

6136

7670

<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:

8772

AN:

152156

Hom.:

367

Cov.:

AF XY:

0.0549

AC XY:

4083

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.103

AC:

4275

AN:

41498

American (AMR)

AF:

0.0858

AC:

1312

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0773

AC:

268

AN:

3468

East Asian (EAS)

AF:

0.00717

AC:

AN:

5160

South Asian (SAS)

AF:

0.0291

AC:

140

AN:

4818

European-Finnish (FIN)

AF:

0.0106

AC:

112

AN:

10612

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0360

AC:

2449

AN:

67986

Other (OTH)

AF:

0.0711

AC:

150

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

420

839

1259

1678

2098

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:

0.0453

Hom.:

Bravo

AF:

0.0669

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.58

PhyloP100

2.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over