rs2523557

Positions:

• chr6-31363480-G-A
• chr6-31363480-G-C
• chr6-31363480-G-T

Variant summary

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

The ENST00000696559.1(HLA-B):​c.-204+2263C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,874 control chromosomes in the GnomAD database, including 36,126 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 0.69 (36126 hom., cov: 30)
• Consequence: HLA-B ENST00000696559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.40

Genes affected

HLA-B (HGNC:4932): (major histocompatibility complex, class I, B) HLA-B belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. Class I molecules play a central role in the immune system by presenting peptides derived from the endoplasmic reticulum lumen. They are expressed in nearly all cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon 1 encodes the leader peptide, exon 2 and 3 encode the alpha1 and alpha2 domains, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region and exons 6 and 7 encode the cytoplasmic tail. Polymorphisms within exon 2 and exon 3 are responsible for the peptide binding specificity of each class one molecule. Typing for these polymorphisms is routinely done for bone marrow and kidney transplantation. Hundreds of HLA-B alleles have been described. [provided by RefSeq, Jul 2008]

DHFRP2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHFRP2		n.31363480G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000696559.1	c.-204+2263C>T		intron_variant				ENSP00000512717.1
HLA-B	ENST00000696560.1	c.-204+2263C>T		intron_variant				ENSP00000512718.1
HLA-B	ENST00000696561.1	c.-299-466C>T		intron_variant				ENSP00000512719.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104058 AN: 151756 Hom.: 36086 Cov.: 30

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.724

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.652

Gnomad OTH AF: 0.681

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

GnomAD4 genome AF: 0.686 AC: 104148 AN: 151874 Hom.: 36126 Cov.: 30 AF XY: 0.696 AC XY: 51652 AN XY: 74230

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.724

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.870

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.764

Gnomad4 NFE AF: 0.652

Gnomad4 OTH AF: 0.684

Alfa AF: 0.662 Hom.: 19225

Bravo AF: 0.676

Asia WGS AF: 0.813 AC: 2827 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.8
DANN	Benign	0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523557; hg19: chr6-31331257;