rs11539216

Positions:

• chr6-32950203-G-A
• chr6-32950203-G-C

Variant summary

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

The NM_006120.4(HLA-DMA):​c.374-314C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0444 in 590,262 control chromosomes in the GnomAD database, including 776 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 0.039 (159 hom., cov: 32)
  • Exomes 𝑓: 0.046 (617 hom.)
• Consequence: HLA-DMA NM_006120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

Genes affected

HLA-DMA (HGNC:4934): (major histocompatibility complex, class II, DM alpha) HLA-DMA belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta chain (DMB), 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 molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-DMA	NM_006120.4	c.374-314C>T		intron_variant		ENST00000374843.9	NP_006111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DMA	ENST00000374843.9	c.374-314C>T		intron_variant			NM_006120.4	ENSP00000363976	P1

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5900 AN: 152190 Hom.: 159 Cov.: 32

Gnomad AFR AF: 0.0119

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0371

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.0345

Gnomad FIN AF: 0.0441

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0588

Gnomad OTH AF: 0.0378

GnomAD4 exome AF: 0.0463 AC: 20283 AN: 437954 Hom.: 617 Cov.: 3 AF XY: 0.0462 AC XY: 10619 AN XY: 229882

Gnomad4 AFR exome AF: 0.0121

Gnomad4 AMR exome AF: 0.0297

Gnomad4 ASJ exome AF: 0.0218

Gnomad4 EAS exome AF: 0.00164

Gnomad4 SAS exome AF: 0.0362

Gnomad4 FIN exome AF: 0.0431

Gnomad4 NFE exome AF: 0.0576

Gnomad4 OTH exome AF: 0.0444

GnomAD4 genome AF: 0.0387 AC: 5899 AN: 152308 Hom.: 159 Cov.: 32 AF XY: 0.0388 AC XY: 2889 AN XY: 74470

Gnomad4 AFR AF: 0.0119

Gnomad4 AMR AF: 0.0370

Gnomad4 ASJ AF: 0.0242

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.0348

Gnomad4 FIN AF: 0.0441

Gnomad4 NFE AF: 0.0588

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0448 Hom.: 85

Bravo AF: 0.0360

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0080
DANN	Benign	0.34

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: rs11539216; hg19: chr6-32917980; COSMIC: COSV100877688; COSMIC: COSV100877688;