rs2523591

chr6-31359183-G-Achr6-31359183-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.-203-1502C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 145,896 control chromosomes in the GnomAD database, including 15,388 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 0.46 (15388 hom., cov: 25)
• Consequence: HLA-B ENST00000696559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 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.-203-1502C>T		intron_variant				P1
HLA-B	ENST00000696560.1	c.-203-1502C>T		intron_variant				P1
HLA-B	ENST00000696561.1	c.-203-1502C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 66431 AN: 145782 Hom.: 15357 Cov.: 25

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.559

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.506

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.471

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

GnomAD4 genome AF: 0.456 AC: 66499 AN: 145896 Hom.: 15388 Cov.: 25 AF XY: 0.466 AC XY: 32894 AN XY: 70646

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.560

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.506

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.466

Alfa AF: 0.432 Hom.: 8007

Bravo AF: 0.443

Asia WGS AF: 0.534 AC: 1857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	4.8
Dann	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523591; hg19: chr6-31326960;