rs2596477

chr6-31359946-G-Achr6-31359946-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.340

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]

ACMG classification

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	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000696559.1	c.-203-2265C>T		intron_variant				P1
HLA-B	ENST00000696560.1	c.-203-2265C>T		intron_variant				P1
HLA-B	ENST00000696561.1	c.-203-2265C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.108 AC: 16369 AN: 152066 Hom.: 1071 Cov.: 33

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

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

Other links and lift over

dbSNP: rs2596477; hg19: chr6-31327723;