6-31359557-G-T

Variant names:

• chr6-31359557-G-T
• rs2523589
• ENST00000696559.1:c.-203-1876C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000696559.1(HLA-B):​c.-203-1876C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,042 control chromosomes in the GnomAD database, including 25,177 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 0.57 (25177 hom., cov: 33)
• Consequence: HLA-B ENST00000696559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.19
• Publications: 59 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 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

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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	ENST00000696559.1		c.-203-1876C>A		intron	N/A	ENSP00000512717.1
	HLA-B	ENST00000696560.1		c.-203-1876C>A		intron	N/A	ENSP00000512718.1
	HLA-B	ENST00000696561.1		c.-203-1876C>A		intron	N/A	ENSP00000512719.1

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86615 AN: 151924 Hom.: 25158 Cov.: 33

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.609

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.628

Gnomad SAS AF: 0.642

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.604

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

GnomAD4 genome AF: 0.570 AC: 86676 AN: 152042 Hom.: 25177 Cov.: 33 AF XY: 0.573 AC XY: 42556 AN XY: 74304

African (AFR) AF: 0.674 AC: 27951 AN: 41450

American (AMR) AF: 0.576 AC: 8811 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1656 AN: 3472

East Asian (EAS) AF: 0.629 AC: 3248 AN: 5166

South Asian (SAS) AF: 0.642 AC: 3092 AN: 4818

European-Finnish (FIN) AF: 0.511 AC: 5378 AN: 10522

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34528 AN: 68006

Other (OTH) AF: 0.598 AC: 1264 AN: 2112

Alfa AF: 0.529 Hom.: 48701

Bravo AF: 0.579

Asia WGS AF: 0.557 AC: 1938 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.15
DANN	Benign	0.59
PhyloP100		-3.2

Splicing

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

Other links and lift over

dbSNP: rs2523589; hg19: chr6-31327334;