6-32950203-G-A

Variant names:

• chr6-32950203-G-A
• rs11539216
• NM_006120.4:c.374-314C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

ENSG00000248993 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006120.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DMA	NM_006120.4	MANE Select	c.374-314C>T		intron	N/A	NP_006111.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DMA	ENST00000374843.9	TSL:6 MANE Select	c.374-314C>T		intron	N/A	ENSP00000363976.4
	ENSG00000248993	ENST00000429234.1	TSL:2	c.88+2746C>T		intron	N/A	ENSP00000412457.1
	HLA-DMA	ENST00000475627.1	TSL:6	n.865C>T		non_coding_transcript_exon	Exon 3 of 3

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

African (AFR) AF: 0.0121 AC: 149 AN: 12300

American (AMR) AF: 0.0297 AC: 531 AN: 17854

Ashkenazi Jewish (ASJ) AF: 0.0218 AC: 297 AN: 13612

East Asian (EAS) AF: 0.00164 AC: 50 AN: 30578

South Asian (SAS) AF: 0.0362 AC: 1531 AN: 42282

European-Finnish (FIN) AF: 0.0431 AC: 1245 AN: 28872

Middle Eastern (MID) AF: 0.0441 AC: 86 AN: 1950

European-Non Finnish (NFE) AF: 0.0576 AC: 15255 AN: 264864

Other (OTH) AF: 0.0444 AC: 1139 AN: 25642

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

African (AFR) AF: 0.0119 AC: 494 AN: 41560

American (AMR) AF: 0.0370 AC: 567 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3470

East Asian (EAS) AF: 0.00405 AC: 21 AN: 5188

South Asian (SAS) AF: 0.0348 AC: 168 AN: 4830

European-Finnish (FIN) AF: 0.0441 AC: 468 AN: 10614

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0588 AC: 3999 AN: 68020

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0475 Hom.: 479

Bravo AF: 0.0360

Asia WGS AF: 0.0160 AC: 56 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0080
DANN	Benign	0.34
PhyloP100		-1.2
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: rs11539216; hg19: chr6-32917980; COSMIC: COSV100877688; COSMIC: COSV100877688;