6-31359287-T-C

Variant names:

• chr6-31359287-T-C
• rs2523590
• ENST00000696559.1:c.-203-1606A>G

Variant summary

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

The ENST00000696559.1(HLA-B):​c.-203-1606A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,890 control chromosomes in the GnomAD database, including 5,153 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 0.25 (5153 hom., cov: 29)
• Consequence: HLA-B ENST00000696559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293
• Publications: 41 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 (NFE) allele frequency at 95% confidence interval = 0.299 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.-203-1606A>G		intron_variant	Intron 2 of 10			ENSP00000512717.1
HLA-B	ENST00000696560.1	c.-203-1606A>G		intron_variant	Intron 1 of 9			ENSP00000512718.1
HLA-B	ENST00000696561.1	c.-203-1606A>G		intron_variant	Intron 3 of 11			ENSP00000512719.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37812 AN: 151772 Hom.: 5147 Cov.: 29

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.380

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.130

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.249 AC: 37843 AN: 151890 Hom.: 5153 Cov.: 29 AF XY: 0.249 AC XY: 18464 AN XY: 74220

African (AFR) AF: 0.165 AC: 6850 AN: 41436

American (AMR) AF: 0.280 AC: 4274 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 615 AN: 3464

East Asian (EAS) AF: 0.130 AC: 673 AN: 5168

South Asian (SAS) AF: 0.294 AC: 1413 AN: 4812

European-Finnish (FIN) AF: 0.243 AC: 2554 AN: 10520

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20555 AN: 67912

Other (OTH) AF: 0.239 AC: 503 AN: 2106

Alfa AF: 0.273 Hom.: 12485

Bravo AF: 0.247

Asia WGS AF: 0.287 AC: 999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.3
DANN	Benign	0.67
PhyloP100		0.29

Splicing

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

Other links and lift over

dbSNP: rs2523590; hg19: chr6-31327064;