6-31356751-G-GTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005514.8(HLA-B):c.279_280insAA(p.Gln94AsnfsTer58) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.43 (5127 hom., cov: 8)
  • Exomes 𝑓: 0.66 (261516 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.53

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 -10 ACMG points.

• BP6: Variant 6-31356751-G-GTT is Benign according to our data. Variant chr6-31356751-G-GTT is described in ClinVar as [Benign]. Clinvar id is 3060726.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.279_280insAA	p.Gln94AsnfsTer58	frameshift_variant	2/8	ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7	c.279_280insAA	p.Gln94AsnfsTer58	frameshift_variant	2/8		NM_005514.8	P1
	ENST00000603274.1	n.105_106insTT		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 15338 AN: 35330 Hom.: 5123 Cov.: 8 FAILED QC

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.700

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.814

Gnomad EAS AF: 0.498

Gnomad SAS AF: 0.471

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.673

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.464

GnomAD3 exomes AF: 0.766 AC: 146712 AN: 191508 Hom.: 62732 AF XY: 0.768 AC XY: 80329 AN XY: 104574

Gnomad AFR exome AF: 0.672

Gnomad AMR exome AF: 0.890

Gnomad ASJ exome AF: 0.883

Gnomad EAS exome AF: 0.691

Gnomad SAS exome AF: 0.826

Gnomad FIN exome AF: 0.742

Gnomad NFE exome AF: 0.722

Gnomad OTH exome AF: 0.765

GnomAD4 exome AF: 0.655 AC: 596345 AN: 910078 Hom.: 261516 Cov.: 19 AF XY: 0.660 AC XY: 298453 AN XY: 452322

Gnomad4 AFR exome AF: 0.503

Gnomad4 AMR exome AF: 0.846

Gnomad4 ASJ exome AF: 0.865

Gnomad4 EAS exome AF: 0.605

Gnomad4 SAS exome AF: 0.776

Gnomad4 FIN exome AF: 0.584

Gnomad4 NFE exome AF: 0.639

Gnomad4 OTH exome AF: 0.671

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.434 AC: 15353 AN: 35362 Hom.: 5127 Cov.: 8 AF XY: 0.430 AC XY: 7192 AN XY: 16738

Gnomad4 AFR AF: 0.291

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.814

Gnomad4 EAS AF: 0.498

Gnomad4 SAS AF: 0.474

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.458

Alfa AF: 0.812 Hom.: 3559

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

HLA-B-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 17, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs749557905; hg19: chr6-31324528;