6-31356061-C-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_005514.8(HLA-B):c.619+106G>C 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 0.72 (18080 hom., cov: 9)
  • Exomes 𝑓: 0.39 (61912 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High AC in GnomAdExome at 129264 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.619+106G>C		intron_variant		ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7	c.619+106G>C		intron_variant			NM_005514.8	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 45823 AN: 63928 Hom.: 18035 Cov.: 9 FAILED QC

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.789

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.901

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.762

GnomAD3 exomes AF: 0.845 AC: 129264 AN: 152902 Hom.: 55390 AF XY: 0.850 AC XY: 70371 AN XY: 82752

Gnomad AFR exome AF: 0.874

Gnomad AMR exome AF: 0.907

Gnomad ASJ exome AF: 0.951

Gnomad EAS exome AF: 0.793

Gnomad SAS exome AF: 0.928

Gnomad FIN exome AF: 0.783

Gnomad NFE exome AF: 0.798

Gnomad OTH exome AF: 0.875

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.389 AC: 134026 AN: 344178 Hom.: 61912 Cov.: 4 AF XY: 0.418 AC XY: 74712 AN XY: 178626

Gnomad4 AFR exome AF: 0.589

Gnomad4 AMR exome AF: 0.670

Gnomad4 ASJ exome AF: 0.692

Gnomad4 EAS exome AF: 0.560

Gnomad4 SAS exome AF: 0.847

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.283

Gnomad4 OTH exome AF: 0.434

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.717 AC: 45919 AN: 64026 Hom.: 18080 Cov.: 9 AF XY: 0.712 AC XY: 21405 AN XY: 30044

Gnomad4 AFR AF: 0.768

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.720

Gnomad4 SAS AF: 0.829

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.768

Alfa AF: 0.806 Hom.: 5045

Asia WGS AF: 0.902 AC: 3138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	9.1
Dann	Benign	0.31

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: rs2596494; hg19: chr6-31323838; COSMIC: COSV69522605; COSMIC: COSV69522605;