rs2523591

Variant names:

• chr6-31359183-G-A
• rs2523591
• ENST00000696559.1:c.-203-1502C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31359183-G-A
• chr6-31359183-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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]

ENSG00000298426 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000696559.1	c.-203-1502C>T		intron_variant	Intron 2 of 10			ENSP00000512717.1
HLA-B	ENST00000696560.1	c.-203-1502C>T		intron_variant	Intron 1 of 9			ENSP00000512718.1
HLA-B	ENST00000696561.1	c.-203-1502C>T		intron_variant	Intron 3 of 11			ENSP00000512719.1

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

African (AFR) AF: 0.457 AC: 17935 AN: 39262

American (AMR) AF: 0.560 AC: 8027 AN: 14344

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 1403 AN: 3414

East Asian (EAS) AF: 0.353 AC: 1707 AN: 4838

South Asian (SAS) AF: 0.609 AC: 2830 AN: 4644

European-Finnish (FIN) AF: 0.506 AC: 4684 AN: 9262

Middle Eastern (MID) AF: 0.584 AC: 160 AN: 274

European-Non Finnish (NFE) AF: 0.424 AC: 28408 AN: 66938

Other (OTH) AF: 0.466 AC: 940 AN: 2018

Alfa AF: 0.439 Hom.: 15588

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
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs2523591; hg19: chr6-31326960;