Genetic Variant ENST00000696559.1:c.-204+2263C>T (chr6-31363480-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 ENST00000696559.1(HLA-B):c.-204+2263C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,874 control chromosomes in the GnomAD database, including 36,126 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 0.69 ( 36126 hom., cov: 30)

Consequence

HLA-B
ENST00000696559.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.40

Publications

19 publications found

Variant links:

Genes affected

HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B 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. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

HLA-B links:

ENSG00000285647 (HGNC:):

ENSG00000285647 links:

DHFRP2 (HGNC:2863): (dihydrofolate reductase pseudogene 2)

DHFRP2 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=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000696559.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
HLA-B	ENST00000696559.1	c.-204+2263C>T	intron	N/A	ENSP00000512717.1
HLA-B	ENST00000696560.1	c.-204+2263C>T	intron	N/A	ENSP00000512718.1
HLA-B	ENST00000696561.1	c.-299-466C>T	intron	N/A	ENSP00000512719.1

Frequencies

GnomAD3 genomes

AF:

0.686

AC:

104058

AN:

151756

Hom.:

36086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.655

Gnomad AMI

AF:

0.744

Gnomad AMR

AF:

0.724

Gnomad ASJ

AF:

0.827

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.818

Gnomad FIN

AF:

0.764

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.652

Gnomad OTH

AF:

0.681

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.686

AC:

104148

AN:

151874

Hom.:

36126

Cov.:

AF XY:

0.696

AC XY:

51652

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.655

AC:

27076

AN:

41356

American (AMR)

AF:

0.724

AC:

11065

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.827

AC:

2870

AN:

3472

East Asian (EAS)

AF:

0.870

AC:

4496

AN:

5170

South Asian (SAS)

AF:

0.818

AC:

3940

AN:

4814

European-Finnish (FIN)

AF:

0.764

AC:

8035

AN:

10520

Middle Eastern (MID)

AF:

0.776

AC:

228

AN:

294

European-Non Finnish (NFE)

AF:

0.652

AC:

44317

AN:

67952

Other (OTH)

AF:

0.684

AC:

1447

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1627

3254

4881

6508

8135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.677

Hom.:

52498

Bravo

AF:

0.676

Asia WGS

AF:

0.813

AC:

2827

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

6.8

(source)

DANN

Benign

0.23

PhyloP100

-2.4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over