rs2769

Positions:

• chr6-31354105-G-A

Variant summary

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

The NM_005514.8(HLA-B):​c.*196C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 452,790 control chromosomes in the GnomAD database, including 1,309 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 0.099 (630 hom., cov: 31)
  • Exomes 𝑓: 0.071 (679 hom.)
• Consequence: HLA-B NM_005514.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.690

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.*196C>T		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.*196C>T		3_prime_UTR_variant	8/8		NM_005514.8	P1

Frequencies

GnomAD3 genomes AF: 0.0992 AC: 14981 AN: 151080 Hom.: 630 Cov.: 31

Gnomad AFR AF: 0.0639

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0651

Gnomad EAS AF: 0.0253

Gnomad SAS AF: 0.0828

Gnomad FIN AF: 0.0591

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.0995

GnomAD4 exome AF: 0.0707 AC: 21331 AN: 301592 Hom.: 679 Cov.: 0 AF XY: 0.0671 AC XY: 10662 AN XY: 159008

Gnomad4 AFR exome AF: 0.0431

Gnomad4 AMR exome AF: 0.0537

Gnomad4 ASJ exome AF: 0.0392

Gnomad4 EAS exome AF: 0.0460

Gnomad4 SAS exome AF: 0.0389

Gnomad4 FIN exome AF: 0.0413

Gnomad4 NFE exome AF: 0.0909

Gnomad4 OTH exome AF: 0.0800

GnomAD4 genome AF: 0.0991 AC: 14984 AN: 151198 Hom.: 630 Cov.: 31 AF XY: 0.0945 AC XY: 6988 AN XY: 73936

Gnomad4 AFR AF: 0.0639

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0651

Gnomad4 EAS AF: 0.0256

Gnomad4 SAS AF: 0.0824

Gnomad4 FIN AF: 0.0591

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.0980

Alfa AF: 0.119 Hom.: 261

Asia WGS AF: 0.0570 AC: 200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	15
DANN	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2769; hg19: chr6-31321882;