rs2070488

Positions:

• chr3-38400999-G-A

Variant summary

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

The NM_005108.4(XYLB):​c.1533+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 1,611,952 control chromosomes in the GnomAD database, including 226,652 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 0.43 (16049 hom., cov: 32)
  • Exomes 𝑓: 0.53 (210603 hom.)
• Consequence: XYLB NM_005108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713

Genes affected

XYLB (HGNC:12839): (xylulokinase) The protein encoded by this gene shares 22% sequence identity with Hemophilus influenzae xylulokinase, and even higher identity to other gene products in C.elegans (45%) and yeast (31-35%), which are thought to belong to a family of enzymes that include fucokinase, gluconokinase, glycerokinase and xylulokinase. These proteins play important roles in energy metabolism. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.559 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
XYLB	NM_005108.4	c.1533+14G>A		intron_variant		ENST00000207870.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
XYLB	ENST00000207870.8	c.1533+14G>A		intron_variant		1	NM_005108.4	P1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65562 AN: 151986 Hom.: 16051 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.564

Gnomad OTH AF: 0.451

GnomAD3 exomes AF: 0.475 AC: 119278 AN: 251274 Hom.: 30325 AF XY: 0.488 AC XY: 66222 AN XY: 135794

Gnomad AFR exome AF: 0.208

Gnomad AMR exome AF: 0.333

Gnomad ASJ exome AF: 0.501

Gnomad EAS exome AF: 0.267

Gnomad SAS exome AF: 0.517

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.564

Gnomad OTH exome AF: 0.496

GnomAD4 exome AF: 0.530 AC: 774181 AN: 1459848 Hom.: 210603 Cov.: 32 AF XY: 0.531 AC XY: 385811 AN XY: 726368

Gnomad4 AFR exome AF: 0.197

Gnomad4 AMR exome AF: 0.339

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.302

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.560

Gnomad4 OTH exome AF: 0.499

GnomAD4 genome AF: 0.431 AC: 65570 AN: 152104 Hom.: 16049 Cov.: 32 AF XY: 0.428 AC XY: 31847 AN XY: 74326

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.506

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.450

Alfa AF: 0.518 Hom.: 27446

Bravo AF: 0.406

Asia WGS AF: 0.399 AC: 1386 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.51
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2070488; hg19: chr3-38442490;