rs2770

Variant names:

• chr6-31354030-G-A
• rs2770
• NM_005514.8:c.*271C>T

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.*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
• Publications: 10 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=-0.92).
• 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 rank	MANE	Protein	UniProt
HLA-B	NM_005514.8	c.*271C>T		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.*271C>T		3_prime_UTR_variant	Exon 8 of 8	6	NM_005514.8	ENSP00000399168.2

Frequencies

GnomAD3 genomes AF: 0.521 AC: 78111 AN: 149830 Hom.: 11449 Cov.: 36

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

African (AFR) AF: 0.505 AC: 3817 AN: 7556

American (AMR) AF: 0.610 AC: 5402 AN: 8850

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 4216 AN: 7994

East Asian (EAS) AF: 0.660 AC: 10617 AN: 16090

South Asian (SAS) AF: 0.561 AC: 13583 AN: 24202

European-Finnish (FIN) AF: 0.582 AC: 9950 AN: 17088

Middle Eastern (MID) AF: 0.492 AC: 712 AN: 1446

European-Non Finnish (NFE) AF: 0.488 AC: 61432 AN: 125836

Other (OTH) AF: 0.499 AC: 6711 AN: 13456

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

African (AFR) AF: 0.515 AC: 21014 AN: 40810

American (AMR) AF: 0.597 AC: 8958 AN: 15008

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1819 AN: 3418

East Asian (EAS) AF: 0.631 AC: 3218 AN: 5102

South Asian (SAS) AF: 0.563 AC: 2652 AN: 4708

European-Finnish (FIN) AF: 0.593 AC: 6175 AN: 10418

Middle Eastern (MID) AF: 0.538 AC: 154 AN: 286

European-Non Finnish (NFE) AF: 0.485 AC: 32602 AN: 67222

Other (OTH) AF: 0.536 AC: 1116 AN: 2082

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
PhyloP100		0.073
RBP_binding_hub_radar		0.92
RBP_regulation_power_radar		2.0
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: rs2770; hg19: chr6-31321807; COSMIC: COSV69520409;