rs3819294

Positions:

• chr6-31354710-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.1013-45C>T variant causes a intron 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 0.027 (49 hom., cov: 8)
  • Exomes 𝑓: 0.072 (3878 hom.)
• Consequence: HLA-B NM_005514.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

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]

HLA-B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8	c.1013-45C>T		intron_variant		ENST00000412585.7	NP_005505.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000412585.7	c.1013-45C>T		intron_variant		6	NM_005514.8	ENSP00000399168.2

Frequencies

GnomAD3 genomes AF: 0.0274 AC: 1646 AN: 60038 Hom.: 49 Cov.: 8

Gnomad AFR AF: 0.0375

Gnomad AMI AF: 0.00195

Gnomad AMR AF: 0.0191

Gnomad ASJ AF: 0.00909

Gnomad EAS AF: 0.0902

Gnomad SAS AF: 0.0239

Gnomad FIN AF: 0.0298

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0220

Gnomad OTH AF: 0.0310

GnomAD3 exomes AF: 0.101 AC: 25227 AN: 250986 Hom.: 1626 AF XY: 0.0965 AC XY: 13091 AN XY: 135662

Gnomad AFR exome AF: 0.136

Gnomad AMR exome AF: 0.0867

Gnomad ASJ exome AF: 0.0207

Gnomad EAS exome AF: 0.254

Gnomad SAS exome AF: 0.0765

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.0816

Gnomad OTH exome AF: 0.0906

GnomAD4 exome AF: 0.0724 AC: 69924 AN: 966006 Hom.: 3878 Cov.: 13 AF XY: 0.0713 AC XY: 35160 AN XY: 493118

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.0798

Gnomad4 ASJ exome AF: 0.0191

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.0723

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.0680

Gnomad4 OTH exome AF: 0.0675

GnomAD4 genome AF: 0.0275 AC: 1651 AN: 60066 Hom.: 49 Cov.: 8 AF XY: 0.0288 AC XY: 816 AN XY: 28286

Gnomad4 AFR AF: 0.0377

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.00909

Gnomad4 EAS AF: 0.0907

Gnomad4 SAS AF: 0.0241

Gnomad4 FIN AF: 0.0298

Gnomad4 NFE AF: 0.0220

Gnomad4 OTH AF: 0.0320

Alfa AF: 0.0799 Hom.: 276

Asia WGS AF: 0.154 AC: 536 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.28

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: rs3819294; hg19: chr6-31322487;