6-31356711-C-CGG

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.319_320insCC(p.Gly107AlafsTer45) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0038 (8 hom., cov: 3)
  • Exomes 𝑓: 0.015 (948 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-B NM_005514.8 frameshift
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.91

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 6-31356711-C-CGG is Benign according to our data. Variant chr6-31356711-C-CGG is described in ClinVar as [Likely_benign]. Clinvar id is 3055858.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 241 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-B	NM_005514.8	c.319_320insCC	p.Gly107AlafsTer45	frameshift_variant	2/8	ENST00000412585.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-B	ENST00000412585.7	c.319_320insCC	p.Gly107AlafsTer45	frameshift_variant	2/8		NM_005514.8	P1
	ENST00000603274.1	n.65_66insGG		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.00376 AC: 241 AN: 64114 Hom.: 8 Cov.: 3

Gnomad AFR AF: 0.00107

Gnomad AMI AF: 0.00266

Gnomad AMR AF: 0.00186

Gnomad ASJ AF: 0.00286

Gnomad EAS AF: 0.0279

Gnomad SAS AF: 0.0208

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00373

Gnomad OTH AF: 0.00125

GnomAD3 exomes AF: 0.0201 AC: 4017 AN: 199372 Hom.: 315 AF XY: 0.0211 AC XY: 2259 AN XY: 107050

Gnomad AFR exome AF: 0.00781

Gnomad AMR exome AF: 0.0103

Gnomad ASJ exome AF: 0.00670

Gnomad EAS exome AF: 0.0646

Gnomad SAS exome AF: 0.0246

Gnomad FIN exome AF: 0.0150

Gnomad NFE exome AF: 0.0188

Gnomad OTH exome AF: 0.0190

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0146 AC: 16140 AN: 1106300 Hom.: 948 Cov.: 30 AF XY: 0.0144 AC XY: 7890 AN XY: 548440

Gnomad4 AFR exome AF: 0.00447

Gnomad4 AMR exome AF: 0.00326

Gnomad4 ASJ exome AF: 0.00324

Gnomad4 EAS exome AF: 0.0249

Gnomad4 SAS exome AF: 0.0145

Gnomad4 FIN exome AF: 0.00205

Gnomad4 NFE exome AF: 0.0159

Gnomad4 OTH exome AF: 0.0145

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00376 AC: 241 AN: 64180 Hom.: 8 Cov.: 3 AF XY: 0.00384 AC XY: 119 AN XY: 30972

Gnomad4 AFR AF: 0.00107

Gnomad4 AMR AF: 0.00186

Gnomad4 ASJ AF: 0.00286

Gnomad4 EAS AF: 0.0280

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.00373

Gnomad4 OTH AF: 0.00122

Alfa AF: 0.0728 Hom.: 407

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

HLA-B-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 17, 2020

This variant is classified as likely 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: rs375356947; hg19: chr6-31324488;