rs2770

Positions:

• chr6-31354030-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.*271C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. 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 0.52 (11483 hom., cov: 36)
  • Exomes 𝑓: 0.52 (17170 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730

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=-0.92).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8	c.*271C>T		3_prime_UTR_variant	8/8	ENST00000412585.7	NP_005505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7	c.*271C>T		3_prime_UTR_variant	8/8		NM_005514.8	ENSP00000399168	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 78111 AN: 149830 Hom.: 11449 Cov.: 36 FAILED QC

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.564

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.536

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.532

GnomAD4 exome AF: 0.523 AC: 116440 AN: 222518 Hom.: 17170 Cov.: 0 AF XY: 0.524 AC XY: 59975 AN XY: 114502

Gnomad4 AFR exome AF: 0.505

Gnomad4 AMR exome AF: 0.610

Gnomad4 ASJ exome AF: 0.527

Gnomad4 EAS exome AF: 0.660

Gnomad4 SAS exome AF: 0.561

Gnomad4 FIN exome AF: 0.582

Gnomad4 NFE exome AF: 0.488

Gnomad4 OTH exome AF: 0.499

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.521 AC: 78197 AN: 149948 Hom.: 11483 Cov.: 36 AF XY: 0.530 AC XY: 38822 AN XY: 73302

Gnomad4 AFR AF: 0.515

Gnomad4 AMR AF: 0.597

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.631

Gnomad4 SAS AF: 0.563

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.485

Gnomad4 OTH AF: 0.536

Alfa AF: 0.493 Hom.: 926

Asia WGS AF: 0.616 AC: 2142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.0
DANN	Benign	0.28
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0

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: rs2770; hg19: chr6-31321807; COSMIC: COSV69520409; COSMIC: COSV69520409;