6-31356866-G-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005514.8(HLA-B):c.165C>G(p.Thr55=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 1,043,632 control chromosomes in the GnomAD database, including 189,939 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 0.36 (6140 hom., cov: 7)
  • Exomes 𝑓: 0.50 (183799 hom.)
• Consequence: HLA-B NM_005514.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP7: Synonymous conserved (PhyloP=-0.077 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.165C>G	p.Thr55=	synonymous_variant	2/8	ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7	c.165C>G	p.Thr55=	synonymous_variant	2/8		NM_005514.8	P1
	ENST00000603274.1	n.220G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.363 AC: 20074 AN: 55258 Hom.: 6136 Cov.: 7

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.514

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.362

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.368

GnomAD3 exomes AF: 0.421 AC: 88536 AN: 210386 Hom.: 25198 AF XY: 0.418 AC XY: 47614 AN XY: 114034

Gnomad AFR exome AF: 0.332

Gnomad AMR exome AF: 0.468

Gnomad ASJ exome AF: 0.525

Gnomad EAS exome AF: 0.419

Gnomad SAS exome AF: 0.365

Gnomad FIN exome AF: 0.358

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.504 AC: 498297 AN: 988308 Hom.: 183799 Cov.: 24 AF XY: 0.502 AC XY: 247327 AN XY: 492314

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.502

Gnomad4 ASJ exome AF: 0.593

Gnomad4 EAS exome AF: 0.499

Gnomad4 SAS exome AF: 0.427

Gnomad4 FIN exome AF: 0.393

Gnomad4 NFE exome AF: 0.518

Gnomad4 OTH exome AF: 0.494

GnomAD4 genome AF: 0.363 AC: 20098 AN: 55324 Hom.: 6140 Cov.: 7 AF XY: 0.344 AC XY: 8900 AN XY: 25872

Gnomad4 AFR AF: 0.203

Gnomad4 AMR AF: 0.399

Gnomad4 ASJ AF: 0.634

Gnomad4 EAS AF: 0.487

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.382

Alfa AF: 0.364 Hom.: 1744

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
Cadd	Benign	9.3
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1050517; hg19: chr6-31324643; COSMIC: COSV69520233; COSMIC: COSV69520233;