rs10751

chr6-32934806-G-A

Variant summary

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

The NM_002118.5(HLA-DMB):c.*165C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 688,032 control chromosomes in the GnomAD database, including 6,804 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 0.13 (1323 hom., cov: 31)
  • Exomes 𝑓: 0.13 (5481 hom.)
• Consequence: HLA-DMB NM_002118.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

Genes affected

HLA-DMB (HGNC:4935): (major histocompatibility complex, class II, DM beta) HLA-DMB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta (DMB) chain, both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP (class II-associated invariant chain peptide) molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 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. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DMB	NM_002118.5	c.*165C>T		3_prime_UTR_variant	6/6	ENST00000418107.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DMB	ENST00000418107.3	c.*165C>T		3_prime_UTR_variant	6/6		NM_002118.5	P1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19170 AN: 151930 Hom.: 1323 Cov.: 31

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.299

Gnomad EAS AF: 0.0783

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.0970

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.155

GnomAD4 exome AF: 0.134 AC: 71685 AN: 535984 Hom.: 5481 Cov.: 7 AF XY: 0.135 AC XY: 38251 AN XY: 282374

Gnomad4 AFR exome AF: 0.0971

Gnomad4 AMR exome AF: 0.139

Gnomad4 ASJ exome AF: 0.301

Gnomad4 EAS exome AF: 0.0935

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.0969

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.149

GnomAD4 genome AF: 0.126 AC: 19168 AN: 152048 Hom.: 1323 Cov.: 31 AF XY: 0.126 AC XY: 9352 AN XY: 74318

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.156

Gnomad4 ASJ AF: 0.299

Gnomad4 EAS AF: 0.0785

Gnomad4 SAS AF: 0.190

Gnomad4 FIN AF: 0.0970

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.153

Alfa AF: 0.133 Hom.: 1956

Bravo AF: 0.129

Asia WGS AF: 0.133 AC: 462 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.6
Dann	Benign	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

Publications

LitVar

Other links and lift over

dbSNP: rs10751; hg19: chr6-32902583;