6-32936123-C-T

Variant names:

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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DMB	NM_002118.5	c.623-471G>A		intron_variant	Intron 3 of 5	ENST00000418107.3	NP_002109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DMB	ENST00000418107.3	c.623-471G>A		intron_variant	Intron 3 of 5	6	NM_002118.5	ENSP00000398890.2

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

Gnomad4 AFR exome AF: 0.569

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.783

Gnomad4 EAS exome AF: 0.752

Gnomad4 SAS exome AF: 0.800

Gnomad4 FIN exome AF: 0.810

Gnomad4 NFE exome AF: 0.753

Gnomad4 OTH exome AF: 0.747

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

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.705

Gnomad4 ASJ AF: 0.845

Gnomad4 EAS AF: 0.783

Gnomad4 SAS AF: 0.849

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.766

Gnomad4 OTH AF: 0.718

Alfa AF: 0.765 Hom.: 78850

Bravo AF: 0.703

Asia WGS AF: 0.803 AC: 2793 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs151719; hg19: chr6-32903900;