rs4988889

Variant names:

• chr6-32667175-G-T
• rs4988889
• ENST00000399084.5:c.-63-505C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000399084.5(HLA-DQB1):​c.-63-505C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 150,474 control chromosomes in the GnomAD database, including 3,156 homozygotes. 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 0.20 (3156 hom., cov: 26)
• Consequence: HLA-DQB1 ENST00000399084.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 6 publications found

Genes affected

HLA-DQB1 (HGNC:4944): (major histocompatibility complex, class II, DQ beta 1) HLA-DQB1 belongs to the HLA class II beta chain paralogs. This class II molecule is a heterodimer consisting of an alpha (DQA) and a beta chain (DQB), 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 (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and it contains six exons. Exon 1 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 DQ molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to four different molecules. Typing for these polymorphisms is routinely done for bone marrow transplantation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DQB1	ENST00000399084.5	c.-63-505C>A		intron_variant	Intron 1 of 5	6		ENSP00000382034.1

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29498 AN: 150354 Hom.: 3154 Cov.: 26

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.0808

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.196 AC: 29504 AN: 150474 Hom.: 3156 Cov.: 26 AF XY: 0.190 AC XY: 13931 AN XY: 73394

African (AFR) AF: 0.210 AC: 8567 AN: 40880

American (AMR) AF: 0.157 AC: 2362 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 566 AN: 3444

East Asian (EAS) AF: 0.0809 AC: 413 AN: 5102

South Asian (SAS) AF: 0.224 AC: 1056 AN: 4716

European-Finnish (FIN) AF: 0.121 AC: 1261 AN: 10400

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14687 AN: 67580

Other (OTH) AF: 0.204 AC: 424 AN: 2078

Alfa AF: 0.206 Hom.: 351

Bravo AF: 0.203

Asia WGS AF: 0.116 AC: 402 AN: 3478

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
PhyloP100		-0.072
PromoterAI		-0.024	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4988889; hg19: chr6-32634952;