rs1050950

Positions:

• chr2-142989280-C-A
• chr2-142989280-C-T

Variant summary

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

The NM_003937.3(KYNU):​c.902+3259C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 636,074 control chromosomes in the GnomAD database, including 20,938 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 0.30 (8349 hom., cov: 32)
  • Exomes 𝑓: 0.22 (12589 hom.)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874

Genes affected

KYNU (HGNC:6469): (kynureninase) Kynureninase is a pyridoxal-5'-phosphate (pyridoxal-P) dependent enzyme that catalyzes the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic acids, respectively. Kynureninase is involved in the biosynthesis of NAD cofactors from tryptophan through the kynurenine pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KYNU	NM_003937.3	c.902+3259C>A		intron_variant		ENST00000264170.9	NP_003928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KYNU	ENST00000264170.9	c.902+3259C>A		intron_variant		1	NM_003937.3	ENSP00000264170.4
KYNU	ENST00000409512.5	c.902+3259C>A		intron_variant		1		ENSP00000386731.1
KYNU	ENST00000375773.6	c.*39-62C>A		intron_variant		1		ENSP00000364928.2

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46121 AN: 151468 Hom.: 8330 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.220 AC: 106718 AN: 484486 Hom.: 12589 AF XY: 0.221 AC XY: 51400 AN XY: 232062

Gnomad4 AFR exome AF: 0.509

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.451

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.203

Gnomad4 NFE exome AF: 0.207

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.305 AC: 46186 AN: 151588 Hom.: 8349 Cov.: 32 AF XY: 0.306 AC XY: 22682 AN XY: 74062

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.277

Alfa AF: 0.214 Hom.: 4910

Bravo AF: 0.311

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.44

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: rs1050950; hg19: chr2-143746849;