ENST00000696559.1:c.-203-1977A>C

Variant names:

• chr6-31359658-T-G
• rs2523586
• ENST00000696559.1:c.-203-1977A>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.-203-1977A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,258 control chromosomes in the GnomAD database, including 3,886 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 0.21 (3886 hom., cov: 33)
• Consequence: HLA-B ENST00000696559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 28 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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 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.-203-1977A>C		intron	N/A	ENSP00000512717.1
	HLA-B	ENST00000696560.1		c.-203-1977A>C		intron	N/A	ENSP00000512718.1
	HLA-B	ENST00000696561.1		c.-203-1977A>C		intron	N/A	ENSP00000512719.1

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32263 AN: 152140 Hom.: 3880 Cov.: 33

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.212 AC: 32290 AN: 152258 Hom.: 3886 Cov.: 33 AF XY: 0.213 AC XY: 15823 AN XY: 74450

African (AFR) AF: 0.116 AC: 4801 AN: 41554

American (AMR) AF: 0.257 AC: 3923 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3468

East Asian (EAS) AF: 0.123 AC: 638 AN: 5190

South Asian (SAS) AF: 0.246 AC: 1188 AN: 4826

European-Finnish (FIN) AF: 0.237 AC: 2513 AN: 10602

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.266 AC: 18074 AN: 68012

Other (OTH) AF: 0.201 AC: 425 AN: 2112

Alfa AF: 0.227 Hom.: 10655

Bravo AF: 0.208

Asia WGS AF: 0.263 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.29

Splicing

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

Other links and lift over

dbSNP: rs2523586; hg19: chr6-31327435;