rs2596574

Positions:

• chr6-31366397-G-A

Variant summary

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

The ENST00000696560.1(HLA-B):​c.-858C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0885 in 1,402,738 control chromosomes in the GnomAD database, including 6,566 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 0.10 (1067 hom., cov: 32)
  • Exomes 𝑓: 0.087 (5499 hom.)
• Consequence: HLA-B ENST00000696560.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138

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=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHFRP2		n.31366397G>A		intragenic_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-B	ENST00000696560.1	c.-858C>T		5_prime_UTR_premature_start_codon_gain_variant	1/10			ENSP00000512718.1
HLA-B	ENST00000696562.1	c.-790C>T		5_prime_UTR_premature_start_codon_gain_variant	1/9			ENSP00000512720.1
HLA-B	ENST00000696560.1	c.-858C>T		5_prime_UTR_variant	1/10			ENSP00000512718.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15563 AN: 151900 Hom.: 1062 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.00778

Gnomad MID AF: 0.135

Gnomad NFE AF: 0.0798

Gnomad OTH AF: 0.147

GnomAD4 exome AF: 0.0869 AC: 108629 AN: 1250720 Hom.: 5499 Cov.: 20 AF XY: 0.0861 AC XY: 54435 AN XY: 632236

Gnomad4 AFR exome AF: 0.171

Gnomad4 AMR exome AF: 0.0999

Gnomad4 ASJ exome AF: 0.0732

Gnomad4 EAS exome AF: 0.0535

Gnomad4 SAS exome AF: 0.0944

Gnomad4 FIN exome AF: 0.00978

Gnomad4 NFE exome AF: 0.0886

Gnomad4 OTH exome AF: 0.0918

GnomAD4 genome AF: 0.103 AC: 15582 AN: 152018 Hom.: 1067 Cov.: 32 AF XY: 0.0990 AC XY: 7358 AN XY: 74292

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.0268

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.00778

Gnomad4 NFE AF: 0.0798

Gnomad4 OTH AF: 0.144

Alfa AF: 0.0821 Hom.: 464

Bravo AF: 0.118

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	15
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2596574; hg19: chr6-31334174;