6-32936824-G-T

Variant summary

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

The NM_002118.5(HLA-DMB):c.622+348C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 213,346 control chromosomes in the GnomAD database, including 37,281 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 0.59 (26711 hom., cov: 28)
  • Exomes 𝑓: 0.58 (10570 hom.)
• Consequence: HLA-DMB NM_002118.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0430

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DMB	NM_002118.5	c.622+348C>A		intron_variant		ENST00000418107.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DMB	ENST00000418107.3	c.622+348C>A		intron_variant			NM_002118.5	P1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89166 AN: 151426 Hom.: 26687 Cov.: 28

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.617

Gnomad OTH AF: 0.575

GnomAD4 exome AF: 0.576 AC: 35586 AN: 61802 Hom.: 10570 Cov.: 0 AF XY: 0.577 AC XY: 17986 AN XY: 31156

Gnomad4 AFR exome AF: 0.561

Gnomad4 AMR exome AF: 0.474

Gnomad4 ASJ exome AF: 0.565

Gnomad4 EAS exome AF: 0.459

Gnomad4 SAS exome AF: 0.507

Gnomad4 FIN exome AF: 0.714

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.544

GnomAD4 genome AF: 0.589 AC: 89228 AN: 151544 Hom.: 26711 Cov.: 28 AF XY: 0.591 AC XY: 43749 AN XY: 74036

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.527

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.400

Gnomad4 SAS AF: 0.514

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.617

Gnomad4 OTH AF: 0.570

Alfa AF: 0.595 Hom.: 46189

Bravo AF: 0.568

Asia WGS AF: 0.472 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.8
Dann	Benign	0.58

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: rs2071556; hg19: chr6-32904601; COSMIC: COSV66870793; COSMIC: COSV66870793;