rs209474

Positions:

• chr6-32956807-A-G

Variant summary

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

The ENST00000422832.1(HLA-DMA):​c.-11-6004T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 151,996 control chromosomes in the GnomAD database, including 11,319 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 0.38 (11319 hom., cov: 31)
• Consequence: HLA-DMA ENST00000422832.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HLA-DMA	ENST00000422832.1	c.-11-6004T>C		intron_variant
HLA-DMA	ENST00000464392.1	n.301-6918T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57414 AN: 151878 Hom.: 11315 Cov.: 31

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.550

Gnomad MID AF: 0.455

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.346

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.378 AC: 57433 AN: 151996 Hom.: 11319 Cov.: 31 AF XY: 0.384 AC XY: 28520 AN XY: 74282

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.353

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.550

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.345

Alfa AF: 0.399 Hom.: 22621

Bravo AF: 0.354

Asia WGS AF: 0.356 AC: 1242 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	0.66
DANN	Benign	0.28

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs209474; hg19: chr6-32924584;