rs1058026

Positions:

• chr6-31353908-A-C

Variant summary

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

The NM_005514.8(HLA-B):​c.*393T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 304,674 control chromosomes in the GnomAD database, including 3,317 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 (2009 hom., cov: 38)
  • Exomes 𝑓: 0.17 (1308 hom.)
• Consequence: HLA-B NM_005514.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.619

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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.282 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.*393T>G		3_prime_UTR_variant	8/8	ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7	c.*393T>G		3_prime_UTR_variant	8/8		NM_005514.8	P1

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32043 AN: 151718 Hom.: 2001 Cov.: 38

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.228

Gnomad MID AF: 0.311

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.240

GnomAD4 exome AF: 0.171 AC: 26191 AN: 152838 Hom.: 1308 Cov.: 0 AF XY: 0.179 AC XY: 13964 AN XY: 78016

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.243

Gnomad4 ASJ exome AF: 0.220

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.211 AC: 32086 AN: 151836 Hom.: 2009 Cov.: 38 AF XY: 0.217 AC XY: 16085 AN XY: 74252

Gnomad4 AFR AF: 0.260

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.255

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.228

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.243

Alfa AF: 0.196 Hom.: 4124

Asia WGS AF: 0.247 AC: 860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1058026; hg19: chr6-31321685;