chr6-32936824-G-T

Variant names:

• chr6-32936824-G-T
• rs2071556
• NM_002118.5:c.622+348C>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.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
• Publications: 34 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.612 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.622+348C>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.622+348C>A		intron	N/A	ENSP00000398890.2	P28068
	HLA-DMB	ENST00000863465.1		c.622+348C>A		intron	N/A	ENSP00000533524.1
	HLA-DMB	ENST00000863464.1		c.481+489C>A		intron	N/A	ENSP00000533523.1

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

African (AFR) AF: 0.561 AC: 1325 AN: 2360

American (AMR) AF: 0.474 AC: 824 AN: 1740

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1530 AN: 2708

East Asian (EAS) AF: 0.459 AC: 2501 AN: 5446

South Asian (SAS) AF: 0.507 AC: 350 AN: 690

European-Finnish (FIN) AF: 0.714 AC: 2515 AN: 3520

Middle Eastern (MID) AF: 0.582 AC: 205 AN: 352

European-Non Finnish (NFE) AF: 0.590 AC: 23948 AN: 40596

Other (OTH) AF: 0.544 AC: 2388 AN: 4390

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

African (AFR) AF: 0.560 AC: 23118 AN: 41260

American (AMR) AF: 0.527 AC: 8042 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2119 AN: 3470

East Asian (EAS) AF: 0.400 AC: 2050 AN: 5130

South Asian (SAS) AF: 0.514 AC: 2468 AN: 4804

European-Finnish (FIN) AF: 0.737 AC: 7761 AN: 10526

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.617 AC: 41857 AN: 67792

Other (OTH) AF: 0.570 AC: 1202 AN: 2108

Alfa AF: 0.601 Hom.: 109688

Bravo AF: 0.568

Asia WGS AF: 0.472 AC: 1645 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.58
PhyloP100		0.043
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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