rs3918148

Positions:

• chr6-32968485-C-G
• chr6-32968485-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000422832.1(HLA-DMA):​c.-12+517G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0237 in 152,458 control chromosomes in the GnomAD database, including 62 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 0.024 (62 hom., cov: 33)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: HLA-DMA ENST00000422832.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508

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]

LOC124901302 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0237 (3605/152364) while in subpopulation SAS AF= 0.0389 (188/4832). AF 95% confidence interval is 0.0344. There are 62 homozygotes in gnomad4. There are 1726 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 62 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124901302	XR_007059545.1	n.37G>C		non_coding_transcript_exon_variant	1/2
LOC124901302	XR_007059546.1	n.37G>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-DMA	ENST00000422832.1	c.-12+517G>C		intron_variant		6		ENSP00000403122.1
HLA-DMA	ENST00000464392.1	n.-41G>C		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0237 AC: 3605 AN: 152246 Hom.: 62 Cov.: 33

Gnomad AFR AF: 0.00649

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0245

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.0241

Gnomad SAS AF: 0.0385

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0351

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.0106 AC: 1 AN: 94 Hom.: 0 Cov.: 0 AF XY: 0.0143 AC XY: 1 AN XY: 70

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0125

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0237 AC: 3605 AN: 152364 Hom.: 62 Cov.: 33 AF XY: 0.0232 AC XY: 1726 AN XY: 74508

Gnomad4 AFR AF: 0.00647

Gnomad4 AMR AF: 0.0244

Gnomad4 ASJ AF: 0.0115

Gnomad4 EAS AF: 0.0239

Gnomad4 SAS AF: 0.0389

Gnomad4 FIN AF: 0.0141

Gnomad4 NFE AF: 0.0351

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0135 Hom.: 6

Bravo AF: 0.0233

Asia WGS AF: 0.0480 AC: 168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.8
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3918148; hg19: chr6-32936262;