rs1058026

Variant names:

• chr6-31353908-A-C
• rs1058026
• NM_005514.8:c.*393T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 32 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=-0.84).
• 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 rank	MANE	Protein	UniProt
HLA-B	NM_005514.8	c.*393T>G		3_prime_UTR_variant	Exon 8 of 8	ENST00000412585.7	NP_005505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7	c.*393T>G		3_prime_UTR_variant	Exon 8 of 8	6	NM_005514.8	ENSP00000399168.2

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

African (AFR) AF: 0.231 AC: 1175 AN: 5086

American (AMR) AF: 0.243 AC: 1521 AN: 6264

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 1493 AN: 6780

East Asian (EAS) AF: 0.260 AC: 3140 AN: 12100

South Asian (SAS) AF: 0.266 AC: 4550 AN: 17082

European-Finnish (FIN) AF: 0.148 AC: 423 AN: 2850

Middle Eastern (MID) AF: 0.251 AC: 198 AN: 788

European-Non Finnish (NFE) AF: 0.132 AC: 12067 AN: 91760

Other (OTH) AF: 0.160 AC: 1624 AN: 10128

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

African (AFR) AF: 0.260 AC: 10753 AN: 41334

American (AMR) AF: 0.249 AC: 3794 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 883 AN: 3460

East Asian (EAS) AF: 0.188 AC: 975 AN: 5180

South Asian (SAS) AF: 0.294 AC: 1414 AN: 4804

European-Finnish (FIN) AF: 0.228 AC: 2418 AN: 10584

Middle Eastern (MID) AF: 0.310 AC: 90 AN: 290

European-Non Finnish (NFE) AF: 0.163 AC: 11055 AN: 67916

Other (OTH) AF: 0.243 AC: 511 AN: 2100

Alfa AF: 0.201 Hom.: 8127

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
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1058026; hg19: chr6-31321685;