ENST00000696559.1:c.-203-866G>A

Variant names:

• chr6-31358547-C-T
• rs2596475
• ENST00000696559.1:c.-203-866G>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.-203-866G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.679 in 151,980 control chromosomes in the GnomAD database, including 35,457 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 0.68 (35457 hom., cov: 32)
• Consequence: HLA-B ENST00000696559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.78 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

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

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-B	ENST00000696559.1		c.-203-866G>A		intron	N/A	ENSP00000512717.1
	HLA-B	ENST00000696560.1		c.-203-866G>A		intron	N/A	ENSP00000512718.1
	HLA-B	ENST00000696561.1		c.-203-866G>A		intron	N/A	ENSP00000512719.1

Frequencies

GnomAD3 genomes AF: 0.679 AC: 103100 AN: 151862 Hom.: 35420 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.726

Gnomad SAS AF: 0.802

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.679 AC: 103189 AN: 151980 Hom.: 35457 Cov.: 32 AF XY: 0.686 AC XY: 50974 AN XY: 74288

African (AFR) AF: 0.743 AC: 30813 AN: 41478

American (AMR) AF: 0.723 AC: 11040 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1900 AN: 3464

East Asian (EAS) AF: 0.726 AC: 3748 AN: 5160

South Asian (SAS) AF: 0.801 AC: 3863 AN: 4820

European-Finnish (FIN) AF: 0.666 AC: 7023 AN: 10546

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42496 AN: 67926

Other (OTH) AF: 0.699 AC: 1474 AN: 2108

Alfa AF: 0.644 Hom.: 4022

Bravo AF: 0.682

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.6
DANN	Benign	0.39
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs2596475; hg19: chr6-31326324;