dbSNP rs1610696: HLA-G:c.*287C>G (chr6-29831026-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000936944.1(HLA-G):c.*209C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 181,036 control chromosomes in the GnomAD database, including 10,406 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 0.28 ( 6269 hom., cov: 33)

Exomes 𝑓: 0.52 ( 4137 hom. )

Consequence

HLA-G
ENST00000936944.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.94

Publications

75 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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new If you want to explore the variant's impact on the transcript ENST00000936944.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.96).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000936944.1. 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.*287C>G	downstream_gene	N/A	NP_001371219.1	Q6DU14
HLA-G	NM_001363567.2		c.*287C>G	downstream_gene	N/A	NP_001350496.1	Q5RJ85
HLA-G	NM_001384280.1		c.*287C>G	downstream_gene	N/A	NP_001371209.1	Q5RJ85

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HLA-G	ENST00000376828.6	TSL:6	c.*287C>G	3_prime_UTR	Exon 8 of 8	ENSP00000366024.2	Q5RJ85
HLA-G	ENST00000936944.1		c.*209C>G	3_prime_UTR	Exon 7 of 7	ENSP00000607003.1
HLA-G	ENST00000376818.7	TSL:6	c.*287C>G	3_prime_UTR	Exon 6 of 6	ENSP00000366014.3	P17693-2

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43264

AN:

152016

Hom.:

6265

Cov.:

show subpopulations

Gnomad AFR

AF:

0.269

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.400

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.297

Gnomad FIN

AF:

0.213

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.310

Gnomad OTH

AF:

0.289

GnomAD4 exome

AF:

0.518

AC:

14975

AN:

28902

Hom.:

4137

Cov.:

AF XY:

0.521

AC XY:

8356

AN XY:

16024

show subpopulations

African (AFR)

AF:

0.545

AC:

363

AN:

666

American (AMR)

AF:

0.445

AC:

1193

AN:

2678

Ashkenazi Jewish (ASJ)

AF:

0.599

AC:

478

AN:

798

East Asian (EAS)

AF:

0.206

AC:

203

AN:

986

South Asian (SAS)

AF:

0.517

AC:

3314

AN:

6406

European-Finnish (FIN)

AF:

0.587

AC:

383

AN:

652

Middle Eastern (MID)

AF:

0.573

AC:

AN:

110

European-Non Finnish (NFE)

AF:

0.543

AC:

8279

AN:

15244

Other (OTH)

AF:

0.513

AC:

699

AN:

1362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.613

Heterozygous variant carriers

218

435

653

870

1088

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

184

276

368

460

<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:

0.285

AC:

43293

AN:

152134

Hom.:

6269

Cov.:

AF XY:

0.280

AC XY:

20812

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.270

AC:

11193

AN:

41508

American (AMR)

AF:

0.289

AC:

4409

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

1388

AN:

3470

East Asian (EAS)

AF:

0.115

AC:

598

AN:

5190

South Asian (SAS)

AF:

0.297

AC:

1435

AN:

4826

European-Finnish (FIN)

AF:

0.213

AC:

2248

AN:

10562

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.310

AC:

21072

AN:

67986

Other (OTH)

AF:

0.286

AC:

603

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1647

3293

4940

6586

8233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<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:

0.303

Hom.:

920

Bravo

AF:

0.290

Asia WGS

AF:

0.191

AC:

668

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.48

(source)

DANN

Benign

0.49

PhyloP100

-1.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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