6-32936123-C-T

Variant names:

• chr6-32936123-C-T
• rs151719
• NM_002118.5:c.623-471G>A

Variant summary

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

The NM_002118.5(HLA-DMB):​c.623-471G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 161,634 control chromosomes in the GnomAD database, including 43,275 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 0.73 (40542 hom., cov: 31)
  • Exomes 𝑓: 0.75 (2733 hom.)
• Consequence: HLA-DMB NM_002118.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.762
• Publications: 44 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002118.5. 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-DMB	NM_002118.5	MANE Select	c.623-471G>A		intron	N/A	NP_002109.2	P28068

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DMB	ENST00000418107.3	TSL:6 MANE Select	c.623-471G>A		intron	N/A	ENSP00000398890.2	P28068
	HLA-DMB	ENST00000863465.1		c.623-519G>A		intron	N/A	ENSP00000533524.1
	HLA-DMB	ENST00000863464.1		c.482-471G>A		intron	N/A	ENSP00000533523.1

Frequencies

GnomAD3 genomes AF: 0.725 AC: 110195 AN: 151942 Hom.: 40528 Cov.: 31

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.830

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.766

Gnomad OTH AF: 0.715

GnomAD4 exome AF: 0.746 AC: 7146 AN: 9574 Hom.: 2733 Cov.: 0 AF XY: 0.761 AC XY: 3815 AN XY: 5014

African (AFR) AF: 0.569 AC: 74 AN: 130

American (AMR) AF: 0.667 AC: 839 AN: 1258

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 130 AN: 166

East Asian (EAS) AF: 0.752 AC: 152 AN: 202

South Asian (SAS) AF: 0.800 AC: 872 AN: 1090

European-Finnish (FIN) AF: 0.810 AC: 196 AN: 242

Middle Eastern (MID) AF: 0.762 AC: 32 AN: 42

European-Non Finnish (NFE) AF: 0.753 AC: 4524 AN: 6006

Other (OTH) AF: 0.747 AC: 327 AN: 438

GnomAD4 genome AF: 0.725 AC: 110244 AN: 152060 Hom.: 40542 Cov.: 31 AF XY: 0.728 AC XY: 54075 AN XY: 74312

African (AFR) AF: 0.600 AC: 24862 AN: 41442

American (AMR) AF: 0.705 AC: 10778 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2930 AN: 3468

East Asian (EAS) AF: 0.783 AC: 4044 AN: 5168

South Asian (SAS) AF: 0.849 AC: 4098 AN: 4826

European-Finnish (FIN) AF: 0.846 AC: 8954 AN: 10580

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.766 AC: 52103 AN: 67978

Other (OTH) AF: 0.718 AC: 1512 AN: 2106

Alfa AF: 0.754 Hom.: 175168

Bravo AF: 0.703

Asia WGS AF: 0.803 AC: 2793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.38
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs151719; hg19: chr6-32903900;