dbSNP rs17875395: HLA-G:c.7-391G>A (chr6-29827445-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_001363567.2(HLA-G):c.7-391G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0433 in 355,054 control chromosomes in the GnomAD database, including 505 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 0.052 ( 288 hom., cov: 32)

Exomes 𝑓: 0.037 ( 217 hom. )

Consequence

HLA-G
NM_001363567.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.314

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0805 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363567.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
HLA-G	NM_001363567.2	c.7-391G>A	intron	N/A	NP_001350496.1	Q5RJ85
HLA-G	NM_001384280.1	c.7-391G>A	intron	N/A	NP_001371209.1	Q5RJ85
HLA-G	NM_002127.6	c.-112-288G>A	intron	N/A	NP_002118.1	P17693-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HLA-G	ENST00000376828.6	TSL:6	c.7-391G>A	intron	N/A	ENSP00000366024.2	Q5RJ85
HCG4P8	ENST00000443049.1	TSL:6	n.920C>T	non_coding_transcript_exon	Exon 1 of 1
HLA-G	ENST00000428701.6	TSL:6	n.67-288G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0517

AC:

7859

AN:

152094

Hom.:

282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0821

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0838

Gnomad ASJ

AF:

0.0772

Gnomad EAS

AF:

0.00753

Gnomad SAS

AF:

0.0286

Gnomad FIN

AF:

0.0105

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0360

Gnomad OTH

AF:

0.0695

GnomAD4 exome

AF:

0.0370

AC:

7508

AN:

202842

Hom.:

217

Cov.:

AF XY:

0.0364

AC XY:

4088

AN XY:

112168

show subpopulations

African (AFR)

AF:

0.0795

AC:

410

AN:

5158

American (AMR)

AF:

0.0851

AC:

841

AN:

9886

Ashkenazi Jewish (ASJ)

AF:

0.0718

AC:

321

AN:

4468

East Asian (EAS)

AF:

0.00327

AC:

AN:

7960

South Asian (SAS)

AF:

0.0353

AC:

1432

AN:

40582

European-Finnish (FIN)

AF:

0.0139

AC:

128

AN:

9190

Middle Eastern (MID)

AF:

0.0962

AC:

176

AN:

1830

European-Non Finnish (NFE)

AF:

0.0331

AC:

3776

AN:

113982

Other (OTH)

AF:

0.0407

AC:

398

AN:

9786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

326

652

978

1304

1630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.0518

AC:

7879

AN:

152212

Hom.:

288

Cov.:

AF XY:

0.0493

AC XY:

3673

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0821

AC:

3411

AN:

41536

American (AMR)

AF:

0.0843

AC:

1289

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0772

AC:

268

AN:

3472

East Asian (EAS)

AF:

0.00755

AC:

AN:

5164

South Asian (SAS)

AF:

0.0290

AC:

140

AN:

4822

European-Finnish (FIN)

AF:

0.0105

AC:

112

AN:

10618

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0360

AC:

2446

AN:

68000

Other (OTH)

AF:

0.0688

AC:

145

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

368

736

1103

1471

1839

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

252

336

420

<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:

0.0409

Hom.:

Bravo

AF:

0.0601

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.66

(source)

DANN

Benign

0.57

PhyloP100

-0.31

PromoterAI

0.0075

Neutral

(source)

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.

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