Genetic Variant NM_001384290.1:c.*94C>T (chr6-29830833-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.*94C>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 0.889 in 431,992 control chromosomes in the GnomAD database, including 171,406 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 0.87 ( 57840 hom., cov: 29)

Exomes 𝑓: 0.90 ( 113566 hom. )

Consequence

HLA-G
NM_001384290.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.608

Publications

60 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=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-G	NM_001384290.1 link	c.*94C>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.*94C>T		3_prime_UTR_variant	Exon 7 of 7	6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.871

AC:

132142

AN:

151790

Hom.:

57781

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

0.852

Gnomad AMR

AF:

0.910

Gnomad ASJ

AF:

0.902

Gnomad EAS

AF:

0.981

Gnomad SAS

AF:

0.880

Gnomad FIN

AF:

0.725

Gnomad MID

AF:

0.905

Gnomad NFE

AF:

0.852

Gnomad OTH

AF:

0.884

GnomAD4 exome

AF:

0.899

AC:

251746

AN:

280084

Hom.:

113566

Cov.:

AF XY:

0.903

AC XY:

143957

AN XY:

159364

show subpopulations

African (AFR)

AF:

0.929

AC:

7711

AN:

8302

American (AMR)

AF:

0.954

AC:

22684

AN:

23770

Ashkenazi Jewish (ASJ)

AF:

0.942

AC:

8236

AN:

8746

East Asian (EAS)

AF:

0.978

AC:

11546

AN:

11800

South Asian (SAS)

AF:

0.926

AC:

50108

AN:

54098

European-Finnish (FIN)

AF:

0.782

AC:

9911

AN:

12678

Middle Eastern (MID)

AF:

0.908

AC:

1488

AN:

1638

European-Non Finnish (NFE)

AF:

0.880

AC:

128269

AN:

145696

Other (OTH)

AF:

0.883

AC:

11793

AN:

13356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.642

Heterozygous variant carriers

709

1418

2128

2837

3546

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.871

AC:

132258

AN:

151908

Hom.:

57840

Cov.:

AF XY:

0.866

AC XY:

64294

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.906

AC:

37530

AN:

41404

American (AMR)

AF:

0.910

AC:

13904

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.902

AC:

3128

AN:

3466

East Asian (EAS)

AF:

0.980

AC:

5053

AN:

5154

South Asian (SAS)

AF:

0.880

AC:

4227

AN:

4804

European-Finnish (FIN)

AF:

0.725

AC:

7652

AN:

10558

Middle Eastern (MID)

AF:

0.901

AC:

265

AN:

294

European-Non Finnish (NFE)

AF:

0.852

AC:

57861

AN:

67934

Other (OTH)

AF:

0.885

AC:

1863

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

822

1645

2467

3290

4112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<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:

0.871

Hom.:

15340

Bravo

AF:

0.889

Asia WGS

AF:

0.932

AC:

3240

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

7.8

(source)

DANN

Benign

0.30

PhyloP100

-0.61

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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