rs2596477

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000696559.1(HLA-B):​c.-203-2265C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 152,184 control chromosomes in the GnomAD database, including 1,071 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 0.11 ( 1071 hom., cov: 33)

Consequence

HLA-B
ENST00000696559.1 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.340
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
HLA-BENST00000696559.1 linkuse as main transcriptc.-203-2265C>T intron_variant ENSP00000512717 P1
HLA-BENST00000696560.1 linkuse as main transcriptc.-203-2265C>T intron_variant ENSP00000512718 P1
HLA-BENST00000696561.1 linkuse as main transcriptc.-203-2265C>T intron_variant ENSP00000512719 P1

Frequencies

GnomAD3 genomes
AF:
0.108
AC:
16369
AN:
152066
Hom.:
1071
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0670
Gnomad AMI
AF:
0.169
Gnomad AMR
AF:
0.114
Gnomad ASJ
AF:
0.0663
Gnomad EAS
AF:
0.0264
Gnomad SAS
AF:
0.0855
Gnomad FIN
AF:
0.0730
Gnomad MID
AF:
0.0350
Gnomad NFE
AF:
0.146
Gnomad OTH
AF:
0.106
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.108
AC:
16373
AN:
152184
Hom.:
1071
Cov.:
33
AF XY:
0.103
AC XY:
7647
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.0670
Gnomad4 AMR
AF:
0.114
Gnomad4 ASJ
AF:
0.0663
Gnomad4 EAS
AF:
0.0266
Gnomad4 SAS
AF:
0.0852
Gnomad4 FIN
AF:
0.0730
Gnomad4 NFE
AF:
0.146
Gnomad4 OTH
AF:
0.105
Alfa
AF:
0.126
Hom.:
508
Bravo
AF:
0.110
Asia WGS
AF:
0.0580
AC:
202
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
7.8
DANN
Benign
0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2596477; hg19: chr6-31327723; API