dbSNP rs1632947: HCG4P8:n.29826881G>A (chr6-29826881-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 variant allele was found at a frequency of 0.494 in 422,470 control chromosomes in the GnomAD database, including 53,524 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 0.49 ( 18125 hom., cov: 31)

Exomes 𝑓: 0.50 ( 35399 hom. )

Consequence

HCG4P8
intragenic

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.653

Publications

27 publications found

Variant links:

COSMIC-nc: COSV64405568

Genes affected

HCG4P8 (HGNC:22927): (HLA complex group 4 pseudogene 8)

HCG4P8 links:

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
HCG4P8		n.29826881G>A	intragenic_variant
HLA-G	NM_001384280.1 link	c.-36-122G>A	intron_variant	Intron 1 of 8	NP_001371209.1
HLA-G	NM_001363567.2 link	c.-158G>A	upstream_gene_variant		NP_001350496.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
HLA-F-AS1	ENST00000849927.1 link	n.26+1590C>T	intron_variant	Intron 1 of 3
HLA-F-AS1	ENST00000849935.1 link	n.230+839C>T	intron_variant	Intron 1 of 2
HLA-G	ENST00000376828.6 link	c.-158G>A	upstream_gene_variant		6	ENSP00000366024.2
HLA-G	ENST00000428701.6 link	n.-98G>A	upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.485

AC:

73664

AN:

151810

Hom.:

18102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.462

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.567

Gnomad EAS

AF:

0.612

Gnomad SAS

AF:

0.665

Gnomad FIN

AF:

0.341

Gnomad MID

AF:

0.586

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.501

GnomAD4 exome

AF:

0.499

AC:

135035

AN:

270542

Hom.:

35399

AF XY:

0.520

AC XY:

78373

AN XY:

150812

show subpopulations

African (AFR)

AF:

0.508

AC:

3653

AN:

7188

American (AMR)

AF:

0.502

AC:

10723

AN:

21340

Ashkenazi Jewish (ASJ)

AF:

0.564

AC:

4514

AN:

8010

East Asian (EAS)

AF:

0.602

AC:

5241

AN:

8706

South Asian (SAS)

AF:

0.666

AC:

34289

AN:

51506

European-Finnish (FIN)

AF:

0.342

AC:

8229

AN:

24064

Middle Eastern (MID)

AF:

0.524

AC:

1350

AN:

2576

European-Non Finnish (NFE)

AF:

0.452

AC:

60971

AN:

134894

Other (OTH)

AF:

0.495

AC:

6065

AN:

12258

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

3021

6042

9063

12084

15105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

484

968

1452

1936

2420

<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:

73727

AN:

151928

Hom.:

18125

Cov.:

AF XY:

0.485

AC XY:

36043

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.510

AC:

21110

AN:

41382

American (AMR)

AF:

0.515

AC:

7859

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.567

AC:

1968

AN:

3468

East Asian (EAS)

AF:

0.611

AC:

3155

AN:

5166

South Asian (SAS)

AF:

0.665

AC:

3204

AN:

4818

European-Finnish (FIN)

AF:

0.341

AC:

3588

AN:

10534

Middle Eastern (MID)

AF:

0.579

AC:

169

AN:

292

European-Non Finnish (NFE)

AF:

0.459

AC:

31187

AN:

67980

Other (OTH)

AF:

0.507

AC:

1067

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1923

3845

5768

7690

9613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

680

1360

2040

2720

3400

<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:

0.472

Hom.:

2188

Bravo

AF:

0.496

Asia WGS

AF:

0.683

AC:

2375

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.97

(source)

DANN

Benign

0.75

PhyloP100

-0.65

PromoterAI

-0.030

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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