dbSNP rs17179108: HLA-G:c.*126C>T (chr6-29830865-C-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.*126C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 390,066 control chromosomes in the GnomAD database, including 5,502 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 0.11 ( 1117 hom., cov: 32)

Exomes 𝑓: 0.15 ( 4385 hom. )

Consequence

HLA-G
NM_001384290.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.316

Publications

58 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=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.*126C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11 link	c.*126C>T		3_prime_UTR_variant	Exon 7 of 7	6	NM_001384290.1	ENSP00000353472.6

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17341

AN:

152064

Hom.:

1107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.0513

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.100

Gnomad OTH

AF:

0.132

GnomAD4 exome

AF:

0.154

AC:

36684

AN:

237884

Hom.:

4385

Cov.:

AF XY:

0.162

AC XY:

21982

AN XY:

135922

show subpopulations

African (AFR)

AF:

0.145

AC:

991

AN:

6812

American (AMR)

AF:

0.182

AC:

3477

AN:

19096

Ashkenazi Jewish (ASJ)

AF:

0.168

AC:

1364

AN:

8096

East Asian (EAS)

AF:

0.216

AC:

1952

AN:

9056

South Asian (SAS)

AF:

0.232

AC:

11489

AN:

49600

European-Finnish (FIN)

AF:

0.0803

AC:

743

AN:

9252

Middle Eastern (MID)

AF:

0.201

AC:

319

AN:

1584

European-Non Finnish (NFE)

AF:

0.119

AC:

14686

AN:

122984

Other (OTH)

AF:

0.146

AC:

1663

AN:

11404

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.617

Heterozygous variant carriers

724

1448

2173

2897

3621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

194

388

582

776

970

<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:

0.114

AC:

17373

AN:

152182

Hom.:

1117

Cov.:

AF XY:

0.114

AC XY:

8466

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.121

AC:

5009

AN:

41502

American (AMR)

AF:

0.140

AC:

2147

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.134

AC:

466

AN:

3470

East Asian (EAS)

AF:

0.199

AC:

1029

AN:

5166

South Asian (SAS)

AF:

0.195

AC:

938

AN:

4810

European-Finnish (FIN)

AF:

0.0513

AC:

544

AN:

10612

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.100

AC:

6821

AN:

68018

Other (OTH)

AF:

0.134

AC:

282

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

761

1521

2282

3042

3803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.108

Hom.:

734

Bravo

AF:

0.120

Asia WGS

AF:

0.195

AC:

675

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

3.1

(source)

DANN

Benign

0.37

PhyloP100

-0.32

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

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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