6-31356824-C-CA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_005514.8(HLA-B):c.206_207insT(p.Glu69AspfsTer30) 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 0.0062 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0098 (495 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.91

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 6-31356824-C-CA is Benign according to our data. Variant chr6-31356824-C-CA is described in ClinVar as [Benign]. Clinvar id is 2656398.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome at 2255 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.206_207insT	p.Glu69AspfsTer30	frameshift_variant	2/8	ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7	c.206_207insT	p.Glu69AspfsTer30	frameshift_variant	2/8		NM_005514.8	P1
	ENST00000603274.1	n.178_179insA		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 406 AN: 65386 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.00419

Gnomad AMI AF: 0.00785

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00979

Gnomad EAS AF: 0.0152

Gnomad SAS AF: 0.00773

Gnomad FIN AF: 0.00347

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00720

Gnomad OTH AF: 0.00536

GnomAD3 exomes AF: 0.0138 AC: 2255 AN: 163622 Hom.: 189 AF XY: 0.0154 AC XY: 1350 AN XY: 87686

Gnomad AFR exome AF: 0.00402

Gnomad AMR exome AF: 0.00938

Gnomad ASJ exome AF: 0.00603

Gnomad EAS exome AF: 0.0214

Gnomad SAS exome AF: 0.0240

Gnomad FIN exome AF: 0.0230

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.0113

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00981 AC: 10438 AN: 1064090 Hom.: 495 Cov.: 27 AF XY: 0.0107 AC XY: 5634 AN XY: 527724

Gnomad4 AFR exome AF: 0.00957

Gnomad4 AMR exome AF: 0.00858

Gnomad4 ASJ exome AF: 0.0105

Gnomad4 EAS exome AF: 0.0370

Gnomad4 SAS exome AF: 0.0348

Gnomad4 FIN exome AF: 0.0101

Gnomad4 NFE exome AF: 0.00711

Gnomad4 OTH exome AF: 0.0131

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00620 AC: 406 AN: 65452 Hom.: 0 Cov.: 0 AF XY: 0.00639 AC XY: 197 AN XY: 30820

Gnomad4 AFR AF: 0.00418

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.00979

Gnomad4 EAS AF: 0.0152

Gnomad4 SAS AF: 0.00765

Gnomad4 FIN AF: 0.00347

Gnomad4 NFE AF: 0.00721

Gnomad4 OTH AF: 0.00525

Alfa AF: 0.0651 Hom.: 572

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

HLA-B: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9281379; hg19: chr6-31324601; COSMIC: COSV69521367; COSMIC: COSV69521367;