chr6-32584178-G-GCC

Variant names:

• chr6-32584178-G-GCC
• rs778205073
• NM_002124.4:c.300_301insGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002124.4(HLA-DRB1):​c.300_301insGG​(p.Arg101GlyfsTer29) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 17)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DRB1 NM_002124.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 3 publications found

Genes affected

HLA-DRB1 (HGNC:4948): (major histocompatibility complex, class II, DR beta 1) HLA-DRB1 belongs to the HLA class II beta chain paralogs. The class II molecule is a heterodimer consisting of an alpha (DRA) and a beta chain (DRB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells. The beta chain is approximately 26-28 kDa. It is encoded by 6 exons. Exon one encodes the leader peptide; exons 2 and 3 encode the two extracellular domains; exon 4 encodes the transmembrane domain; and exon 5 encodes the cytoplasmic tail. Within the DR molecule the beta chain contains all the polymorphisms specifying the peptide binding specificities. Hundreds of DRB1 alleles have been described and some alleles have increased frequencies associated with certain diseases or conditions. For example, DRB1*1302 has been related to acute and chronic hepatitis B virus persistence. There are multiple pseudogenes of this gene. [provided by RefSeq, Jul 2020]

HLA-DRB1 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002124.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRB1	NM_002124.4	MANE Select	c.300_301insGG	p.Arg101GlyfsTer29	frameshift	Exon 2 of 6	NP_002115.2	P01911

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRB1	ENST00000360004.6	TSL:6 MANE Select	c.300_301insGG	p.Arg101GlyfsTer29	frameshift	Exon 2 of 6	ENSP00000353099.5	P01911
	HLA-DRB1	ENST00000963203.1		c.378_379insGG	p.Arg127GlyfsTer29	frameshift	Exon 2 of 6	ENSP00000633262.1
	HLA-DRB1	ENST00000859900.1		c.300_301insGG	p.Arg101GlyfsTer29	frameshift	Exon 2 of 5	ENSP00000529959.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 48392 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 536484 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 267512

African (AFR) AF: 0.00 AC: 0 AN: 15900

American (AMR) AF: 0.00 AC: 0 AN: 16576

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10706

East Asian (EAS) AF: 0.00 AC: 0 AN: 11112

South Asian (SAS) AF: 0.00 AC: 0 AN: 31566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1864

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 401268

Other (OTH) AF: 0.00 AC: 0 AN: 22864

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 48392 Hom.: 0 Cov.: 17 AF XY: 0.00 AC XY: 0 AN XY: 23596

African (AFR) AF: 0.00 AC: 0 AN: 13608

American (AMR) AF: 0.00 AC: 0 AN: 4406

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1160

East Asian (EAS) AF: 0.00 AC: 0 AN: 1072

South Asian (SAS) AF: 0.00 AC: 0 AN: 1430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3988

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 62

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 21822

Other (OTH) AF: 0.00 AC: 0 AN: 622

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.1
Mutation Taster		=195/5	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs778205073; hg19: chr6-32551955;