6-31355632-T-C

Position:

• chr6-31355632-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_005514.8(HLA-B):​c.620-40A>G 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 0.65 (12111 hom., cov: 8)
  • Exomes 𝑓: 0.78 (336672 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.11

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-B	NM_005514.8	c.620-40A>G		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.620-40A>G		intron_variant		6	NM_005514.8	ENSP00000399168.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 32187 AN: 49434 Hom.: 12071 Cov.: 8 FAILED QC

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.876

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.840

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.702

GnomAD3 exomes AF: 0.850 AC: 212330 AN: 249770 Hom.: 90803 AF XY: 0.855 AC XY: 115404 AN XY: 135032

Gnomad AFR exome AF: 0.888

Gnomad AMR exome AF: 0.908

Gnomad ASJ exome AF: 0.949

Gnomad EAS exome AF: 0.804

Gnomad SAS exome AF: 0.925

Gnomad FIN exome AF: 0.802

Gnomad NFE exome AF: 0.814

Gnomad OTH exome AF: 0.868

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.778 AC: 763767 AN: 982264 Hom.: 336672 Cov.: 20 AF XY: 0.785 AC XY: 388838 AN XY: 495138

Gnomad4 AFR exome AF: 0.866

Gnomad4 AMR exome AF: 0.900

Gnomad4 ASJ exome AF: 0.945

Gnomad4 EAS exome AF: 0.835

Gnomad4 SAS exome AF: 0.928

Gnomad4 FIN exome AF: 0.767

Gnomad4 NFE exome AF: 0.746

Gnomad4 OTH exome AF: 0.809

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.652 AC: 32266 AN: 49510 Hom.: 12111 Cov.: 8 AF XY: 0.643 AC XY: 14899 AN XY: 23160

Gnomad4 AFR AF: 0.686

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.876

Gnomad4 EAS AF: 0.592

Gnomad4 SAS AF: 0.780

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.711

Alfa AF: 0.831 Hom.: 18751

Asia WGS AF: 0.902 AC: 3137 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.2
DANN	Benign	0.57

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: rs2523605; hg19: chr6-31323409;