NM_002121.6:c.101-1418T>C

Variant names:

• chr6-33079254-T-C
• rs1431403
• NM_002121.6:c.101-1418T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002121.6(HLA-DPB1):​c.101-1418T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 152,158 control chromosomes in the GnomAD database, including 11,633 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 0.37 (11633 hom., cov: 32)
• Consequence: HLA-DPB1 NM_002121.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.911
• Publications: 48 publications found

Genes affected

HLA-DPB1 (HGNC:4940): (major histocompatibility complex, class II, DP beta 1) HLA-DPB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta chain (DPB), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. 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. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. [provided by RefSeq, Jul 2008]

HLA-DPA1 (HGNC:4938): (major histocompatibility complex, class II, DP alpha 1) HLA-DPA1 belongs to the HLA class II alpha chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DPA) and a beta (DPB) chain, both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. 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. Within the DP molecule both the alpha chain and the beta chain contain the polymorphisms specifying the peptide binding specificities, resulting in up to 4 different molecules. [provided by RefSeq, Jul 2008]

RPL32P1 (HGNC:10339): (ribosomal protein L32 pseudogene 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002121.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPB1	NM_002121.6	MANE Select	c.101-1418T>C		intron	N/A	NP_002112.3
	HLA-DPA1	NM_001242524.2		c.-100+1426A>G		intron	N/A	NP_001229453.1	P20036
	HLA-DPA1	NM_001242525.2		c.-24+1426A>G		intron	N/A	NP_001229454.1	X5CKE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HLA-DPB1	ENST00000418931.7	TSL:6 MANE Select	c.101-1418T>C		intron	N/A	ENSP00000408146.2	P04440
	HLA-DPB1	ENST00000966804.1		c.101-1418T>C		intron	N/A	ENSP00000636863.1
	HLA-DPA1	ENST00000419277.5	TSL:6	c.-100+1426A>G		intron	N/A	ENSP00000393566.1	P20036

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55782 AN: 152040 Hom.: 11617 Cov.: 32

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.372

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

GnomAD4 genome AF: 0.367 AC: 55818 AN: 152158 Hom.: 11633 Cov.: 32 AF XY: 0.361 AC XY: 26832 AN XY: 74390

African (AFR) AF: 0.539 AC: 22372 AN: 41486

American (AMR) AF: 0.291 AC: 4456 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 628 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3591 AN: 5180

South Asian (SAS) AF: 0.328 AC: 1580 AN: 4824

European-Finnish (FIN) AF: 0.245 AC: 2595 AN: 10594

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19588 AN: 67998

Other (OTH) AF: 0.380 AC: 800 AN: 2108

Alfa AF: 0.313 Hom.: 30954

Bravo AF: 0.376

Asia WGS AF: 0.492 AC: 1711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-0.91
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: rs1431403; hg19: chr6-33047031; COSMIC: COSV69603046; COSMIC: COSV69603046;