6-32581624-T-G

Variant names:

• chr6-32581624-T-G
• rs701831
• NM_002124.4:c.585A>C

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.585A>C​(p.Arg195Arg) 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: 𝑓 0.0 (0 hom., cov: 7)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HLA-DRB1 NM_002124.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.465
• Publications: 20 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=-0.66).
• BP7: Synonymous conserved (PhyloP=0.465 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.585A>C	p.Arg195Arg	synonymous	Exon 3 of 6	NP_002115.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DRB1	ENST00000360004.6	TSL:6 MANE Select	c.585A>C	p.Arg195Arg	synonymous	Exon 3 of 6	ENSP00000353099.5
	HLA-DRB1	ENST00000963203.1		c.663A>C	p.Arg221Arg	synonymous	Exon 3 of 6	ENSP00000633262.1
	HLA-DRB1	ENST00000859900.1		c.585A>C	p.Arg195Arg	synonymous	Exon 3 of 5	ENSP00000529959.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 49978 Hom.: 0 Cov.: 7

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 AF: 0.00 AC: 0 AN: 1115522 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 560738

African (AFR) AF: 0.00 AC: 0 AN: 23762

American (AMR) AF: 0.00 AC: 0 AN: 38624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20610

East Asian (EAS) AF: 0.00 AC: 0 AN: 32418

South Asian (SAS) AF: 0.00 AC: 0 AN: 69342

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4196

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 837492

Other (OTH) AF: 0.00 AC: 0 AN: 45820

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 49978 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 23914

African (AFR) AF: 0.00 AC: 0 AN: 12126

American (AMR) AF: 0.00 AC: 0 AN: 4230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1072

East Asian (EAS) AF: 0.00 AC: 0 AN: 2036

South Asian (SAS) AF: 0.00 AC: 0 AN: 1612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2938

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 72

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 24950

Other (OTH) AF: 0.00 AC: 0 AN: 588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	13
DANN	Benign	0.63
PhyloP100		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs701831; hg19: chr6-32549401;