6-32579276-A-G

Position:

• chr6-32579276-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002124.4(HLA-DRB1):​c.788-172T>C variant causes a intron 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 0.19 (1734 hom., cov: 6)
• Consequence: HLA-DRB1 NM_002124.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DRB1	NM_002124.4	c.788-172T>C		intron_variant		ENST00000360004.6	NP_002115.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DRB1	ENST00000360004.6	c.788-172T>C		intron_variant		6	NM_002124.4	ENSP00000353099.5

Frequencies

GnomAD3 genomes AF: 0.187 AC: 8338 AN: 44640 Hom.: 1731 Cov.: 6

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0854

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.208

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.187 AC: 8344 AN: 44678 Hom.: 1734 Cov.: 6 AF XY: 0.184 AC XY: 3985 AN XY: 21696

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.198

Gnomad4 SAS AF: 0.175

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.177

Gnomad4 OTH AF: 0.203

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs9269701; hg19: chr6-32547053;