rs2523608

chr6-31354782-G-Achr6-31354782-G-Cchr6-31354782-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005514.8(HLA-B):c.1013-117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 411,130 control chromosomes in the GnomAD database, including 48,187 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 0.19 (1019 hom., cov: 7)
  • Exomes 𝑓: 0.44 (47168 hom.)
• Consequence: HLA-B NM_005514.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.1013-117C>T		intron_variant		ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7	c.1013-117C>T		intron_variant			NM_005514.8	P1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 8670 AN: 46832 Hom.: 1013 Cov.: 7

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.109

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.442 AC: 160943 AN: 364272 Hom.: 47168 Cov.: 6 AF XY: 0.459 AC XY: 88875 AN XY: 193654

Gnomad4 AFR exome AF: 0.529

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.406

Gnomad4 EAS exome AF: 0.262

Gnomad4 SAS exome AF: 0.689

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.410

Gnomad4 OTH exome AF: 0.439

GnomAD4 genome AF: 0.185 AC: 8684 AN: 46858 Hom.: 1019 Cov.: 7 AF XY: 0.177 AC XY: 3922 AN XY: 22196

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.192

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.195

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.164

Alfa AF: 0.595 Hom.: 46219

Asia WGS AF: 0.633 AC: 2201 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	8.0
Dann	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523608; hg19: chr6-31322559;