dbSNP rs41557518: HLA-G:p.Leu154CysfsTer60 (chr6-29828657-AC-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001384290.1(HLA-G):c.460delC(p.Leu154CysfsTer60) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 1,613,460 control chromosomes in the GnomAD database, including 347 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.028 ( 101 hom., cov: 32)

Exomes 𝑓: 0.013 ( 246 hom. )

Consequence

HLA-G
NM_001384290.1 frameshift

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.527

Publications

16 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.460delC	p.Leu154CysfsTer60	frameshift_variant	Exon 3 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.460delC	p.Leu154CysfsTer60	frameshift_variant	Exon 3 of 7	6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4276

AN:

152178

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0686

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0182

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.0194

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.00245

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.0330

GnomAD2 exomes

AF:

0.0167

AC:

4149

AN:

247946

AF XY:

0.0164

show subpopulations

Gnomad AFR exome

AF:

0.0702

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.0218

Gnomad EAS exome

AF:

0.0189

Gnomad FIN exome

AF:

0.00176

Gnomad NFE exome

AF:

0.0127

Gnomad OTH exome

AF:

0.0187

GnomAD4 exome

AF:

0.0130

AC:

18956

AN:

1461164

Hom.:

246

Cov.:

AF XY:

0.0131

AC XY:

9543

AN XY:

726922

show subpopulations

African (AFR)

AF:

0.0741

AC:

2482

AN:

33480

American (AMR)

AF:

0.0146

AC:

651

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0203

AC:

530

AN:

26136

East Asian (EAS)

AF:

0.0115

AC:

457

AN:

39700

South Asian (SAS)

AF:

0.0149

AC:

1281

AN:

86258

European-Finnish (FIN)

AF:

0.00199

AC:

105

AN:

52698

Middle Eastern (MID)

AF:

0.0328

AC:

189

AN:

5768

European-Non Finnish (NFE)

AF:

0.0110

AC:

12204

AN:

1112008

Other (OTH)

AF:

0.0175

AC:

1057

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

1230

2461

3691

4922

6152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

494

988

1482

1976

2470

<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:

0.0281

AC:

4275

AN:

152296

Hom.:

101

Cov.:

AF XY:

0.0275

AC XY:

2045

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0685

AC:

2845

AN:

41562

American (AMR)

AF:

0.0181

AC:

277

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

AN:

3470

East Asian (EAS)

AF:

0.0195

AC:

101

AN:

5182

South Asian (SAS)

AF:

0.0110

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00245

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0122

AC:

830

AN:

68004

Other (OTH)

AF:

0.0322

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

216

432

649

865

1081

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.00668

Hom.:

Bravo

AF:

0.0332

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.0161

EpiControl

AF:

0.0168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.53

Mutation Taster

=195/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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