6-32584314-G-A

Variant names:

• chr6-32584314-G-A
• rs1059572
• NM_002124.4:c.165C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_002124.4(HLA-DRB1):​c.165C>T​(p.Phe55Phe) variant causes a synonymous 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: not found (cov: 20)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DRB1 NM_002124.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 15 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-2.12 with no splicing effect.

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.165C>T	p.Phe55Phe	synonymous	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.165C>T	p.Phe55Phe	synonymous	Exon 2 of 6	ENSP00000353099.5	P01911
	HLA-DRB1	ENST00000963203.1		c.243C>T	p.Phe81Phe	synonymous	Exon 2 of 6	ENSP00000633262.1
	HLA-DRB1	ENST00000859900.1		c.165C>T	p.Phe55Phe	synonymous	Exon 2 of 5	ENSP00000529959.1

Frequencies

GnomAD3 genomes Cov.: 20

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 8.32e-7 AC: 1 AN: 1201668 Hom.: 0 Cov.: 31 AF XY: 0.00000165 AC XY: 1 AN XY: 606664

African (AFR) AF: 0.00 AC: 0 AN: 30446

American (AMR) AF: 0.00 AC: 0 AN: 43516

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24492

East Asian (EAS) AF: 0.00 AC: 0 AN: 37374

South Asian (SAS) AF: 0.00 AC: 0 AN: 81432

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5438

European-Non Finnish (NFE) AF: 0.00000114 AC: 1 AN: 877842

Other (OTH) AF: 0.00 AC: 0 AN: 51652

GnomAD4 genome Cov.: 20

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.2
DANN	Benign	0.55
PhyloP100		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1059572; hg19: chr6-32552091;