rs2523546

Positions:

• chr6-31365143-G-A

Variant summary

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

The ENST00000696559.1(HLA-B):​c.-204+600C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0783 in 152,136 control chromosomes in the GnomAD database, including 629 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 0.078 (629 hom., cov: 33)
• Consequence: HLA-B ENST00000696559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.881

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHFRP2		n.31365143G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000696559.1	c.-204+600C>T		intron_variant				ENSP00000512717.1
HLA-B	ENST00000696560.1	c.-204+600C>T		intron_variant				ENSP00000512718.1
HLA-B	ENST00000696561.1	c.-300+600C>T		intron_variant				ENSP00000512719.1

Frequencies

GnomAD3 genomes AF: 0.0783 AC: 11908 AN: 152018 Hom.: 629 Cov.: 33

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0391

Gnomad ASJ AF: 0.0452

Gnomad EAS AF: 0.00481

Gnomad SAS AF: 0.0620

Gnomad FIN AF: 0.0863

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0600

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

GnomAD4 genome AF: 0.0783 AC: 11911 AN: 152136 Hom.: 629 Cov.: 33 AF XY: 0.0740 AC XY: 5503 AN XY: 74404

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.0390

Gnomad4 ASJ AF: 0.0452

Gnomad4 EAS AF: 0.00463

Gnomad4 SAS AF: 0.0630

Gnomad4 FIN AF: 0.0863

Gnomad4 NFE AF: 0.119

Gnomad4 OTH AF: 0.0594

Alfa AF: 0.101 Hom.: 109

Bravo AF: 0.0720

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	8.1
DANN	Benign	0.42

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2523546; hg19: chr6-31332920;