Genetic Variant HLA-G:c.344-14G>A (chr6-29828529-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_001384290.1(HLA-G):c.344-14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,608,644 control chromosomes in the GnomAD database, including 192,152 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 0.48 ( 18074 hom., cov: 31)

Exomes 𝑓: 0.48 ( 174078 hom. )

Consequence

HLA-G
NM_001384290.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.184

Publications

11 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=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.647 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.344-14G>A	intron	N/A	NP_001371219.1	Q6DU14
HLA-G	NM_001363567.2		c.359-14G>A	intron	N/A	NP_001350496.1	Q5RJ85
HLA-G	NM_001384280.1		c.359-14G>A	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.344-14G>A	intron	N/A	ENSP00000353472.6	P17693-1
HLA-G	ENST00000376828.6	TSL:6	c.359-14G>A	intron	N/A	ENSP00000366024.2	Q5RJ85
HLA-G	ENST00000936944.1		c.344-14G>A	intron	N/A	ENSP00000607003.1

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73519

AN:

151654

Hom.:

18050

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.514

Gnomad ASJ

AF:

0.568

Gnomad EAS

AF:

0.610

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.340

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.460

Gnomad OTH

AF:

0.498

GnomAD2 exomes

AF:

0.499

AC:

121266

AN:

243216

AF XY:

0.508

show subpopulations

Gnomad AFR exome

AF:

0.512

Gnomad AMR exome

AF:

0.500

Gnomad ASJ exome

AF:

0.576

Gnomad EAS exome

AF:

0.599

Gnomad FIN exome

AF:

0.337

Gnomad NFE exome

AF:

0.455

Gnomad OTH exome

AF:

0.496

GnomAD4 exome

AF:

0.483

AC:

703283

AN:

1456872

Hom.:

174078

Cov.:

AF XY:

0.490

AC XY:

354630

AN XY:

724190

show subpopulations

African (AFR)

AF:

0.510

AC:

17040

AN:

33414

American (AMR)

AF:

0.504

AC:

22475

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.574

AC:

14871

AN:

25904

East Asian (EAS)

AF:

0.655

AC:

25981

AN:

39654

South Asian (SAS)

AF:

0.672

AC:

57844

AN:

86132

European-Finnish (FIN)

AF:

0.346

AC:

18031

AN:

52056

Middle Eastern (MID)

AF:

0.562

AC:

3227

AN:

5746

European-Non Finnish (NFE)

AF:

0.462

AC:

512959

AN:

1109164

Other (OTH)

AF:

0.513

AC:

30855

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

18474

36947

55421

73894

92368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15530

31060

46590

62120

77650

<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:

0.485

AC:

73583

AN:

151772

Hom.:

18074

Cov.:

AF XY:

0.485

AC XY:

35945

AN XY:

74156

show subpopulations

African (AFR)

AF:

0.508

AC:

21020

AN:

41368

American (AMR)

AF:

0.514

AC:

7847

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.568

AC:

1970

AN:

3468

East Asian (EAS)

AF:

0.609

AC:

3109

AN:

5102

South Asian (SAS)

AF:

0.667

AC:

3209

AN:

4814

European-Finnish (FIN)

AF:

0.340

AC:

3586

AN:

10560

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.460

AC:

31189

AN:

67868

Other (OTH)

AF:

0.503

AC:

1062

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1903

3806

5709

7612

9515

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

678

1356

2034

2712

3390

<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:

0.480

Hom.:

3293

Bravo

AF:

0.496

Asia WGS

AF:

0.685

AC:

2382

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

-0.18

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over