rs714289

Variant names:

• chr6-32938034-A-G
• rs714289
• NM_002118.5:c.338-578T>C

Variant summary

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

The NM_002118.5(HLA-DMB):​c.338-578T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0624 in 153,212 control chromosomes in the GnomAD database, including 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 0.062 (315 hom., cov: 32)
  • Exomes 𝑓: 0.048 (4 hom.)
• Consequence: HLA-DMB NM_002118.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.282

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]

ENSG00000248993 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HLA-DMB	NM_002118.5	c.338-578T>C		intron_variant	Intron 2 of 5	ENST00000418107.3	NP_002109.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HLA-DMB	ENST00000418107.3	c.338-578T>C		intron_variant	Intron 2 of 5	6	NM_002118.5	ENSP00000398890.2
ENSG00000248993	ENST00000429234.1	c.434-578T>C		intron_variant	Intron 3 of 3	2		ENSP00000412457.1
HLA-DMB	ENST00000414017.5	c.5-578T>C		intron_variant	Intron 1 of 3	6		ENSP00000411276.1
HLA-DMB	ENST00000498020.1	n.1164T>C		non_coding_transcript_exon_variant	Exon 2 of 2	6

Frequencies

GnomAD3 genomes AF: 0.0625 AC: 9508 AN: 152118 Hom.: 315 Cov.: 32

Gnomad AFR AF: 0.0854

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0536

Gnomad ASJ AF: 0.0294

Gnomad EAS AF: 0.00500

Gnomad SAS AF: 0.0442

Gnomad FIN AF: 0.0447

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0614

Gnomad OTH AF: 0.0593

GnomAD4 exome AF: 0.0482 AC: 47 AN: 976 Hom.: 4 Cov.: 0 AF XY: 0.0508 AC XY: 25 AN XY: 492

Gnomad4 AFR exome AF: 0.0714

Gnomad4 AMR exome AF: 0.0208

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0596

Gnomad4 OTH exome AF: 0.0217

GnomAD4 genome AF: 0.0625 AC: 9511 AN: 152236 Hom.: 315 Cov.: 32 AF XY: 0.0615 AC XY: 4577 AN XY: 74426

Gnomad4 AFR AF: 0.0853

Gnomad4 AMR AF: 0.0536

Gnomad4 ASJ AF: 0.0294

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.0444

Gnomad4 FIN AF: 0.0447

Gnomad4 NFE AF: 0.0614

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0577 Hom.: 497

Bravo AF: 0.0634

Asia WGS AF: 0.0250 AC: 86 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs714289; hg19: chr6-32905811;