6-31357052-G-C

Position:

• chr6-31357052-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005514.8(HLA-B):​c.73+34C>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 0.056 (327 hom., cov: 3)
  • Exomes 𝑓: 0.12 (39799 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.73+34C>G		intron_variant		ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7	c.73+34C>G		intron_variant			NM_005514.8	P1
	ENST00000603274.1	n.406G>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0559 AC: 2350 AN: 42020 Hom.: 326 Cov.: 3

Gnomad AFR AF: 0.0415

Gnomad AMI AF: 0.0444

Gnomad AMR AF: 0.0489

Gnomad ASJ AF: 0.0474

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.120

Gnomad FIN AF: 0.0246

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.0596

Gnomad OTH AF: 0.0698

GnomAD3 exomes AF: 0.637 AC: 95424 AN: 149916 Hom.: 39061 AF XY: 0.645 AC XY: 53175 AN XY: 82384

Gnomad AFR exome AF: 0.693

Gnomad AMR exome AF: 0.631

Gnomad ASJ exome AF: 0.533

Gnomad EAS exome AF: 0.886

Gnomad SAS exome AF: 0.789

Gnomad FIN exome AF: 0.616

Gnomad NFE exome AF: 0.542

Gnomad OTH exome AF: 0.638

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.122 AC: 87109 AN: 714552 Hom.: 39799 Cov.: 16 AF XY: 0.134 AC XY: 47778 AN XY: 355824

Gnomad4 AFR exome AF: 0.162

Gnomad4 AMR exome AF: 0.166

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.556

Gnomad4 SAS exome AF: 0.447

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.0813

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.0558 AC: 2347 AN: 42038 Hom.: 327 Cov.: 3 AF XY: 0.0510 AC XY: 1024 AN XY: 20060

Gnomad4 AFR AF: 0.0414

Gnomad4 AMR AF: 0.0489

Gnomad4 ASJ AF: 0.0474

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0246

Gnomad4 NFE AF: 0.0595

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.329 Hom.: 943

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.5
DANN	Benign	0.46

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: rs9266196; hg19: chr6-31324829; COSMIC: COSV69520315; COSMIC: COSV69520315;