rs1050951

Positions:

• chr2-142989395-G-A

Variant summary

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

The NM_001032998.2(KYNU):​c.*92G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 988,814 control chromosomes in the GnomAD database, including 7,614 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 0.11 (1078 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6536 hom.)
• Consequence: KYNU NM_001032998.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14

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=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KYNU	NM_003937.3	c.902+3374G>A		intron_variant		ENST00000264170.9	NP_003928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KYNU	ENST00000375773.6	c.*92G>A		3_prime_UTR_variant	12/12	1		ENSP00000364928.2
KYNU	ENST00000264170.9	c.902+3374G>A		intron_variant		1	NM_003937.3	ENSP00000264170.4
KYNU	ENST00000409512.5	c.902+3374G>A		intron_variant		1		ENSP00000386731.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17331 AN: 151730 Hom.: 1076 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0650

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0721

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.123 AC: 102926 AN: 836966 Hom.: 6536 Cov.: 26 AF XY: 0.122 AC XY: 47393 AN XY: 386890

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.0824

Gnomad4 ASJ exome AF: 0.0634

Gnomad4 EAS exome AF: 0.280

Gnomad4 SAS exome AF: 0.129

Gnomad4 FIN exome AF: 0.0641

Gnomad4 NFE exome AF: 0.123

Gnomad4 OTH exome AF: 0.133

GnomAD4 genome AF: 0.114 AC: 17343 AN: 151848 Hom.: 1078 Cov.: 32 AF XY: 0.113 AC XY: 8352 AN XY: 74234

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0916

Gnomad4 ASJ AF: 0.0650

Gnomad4 EAS AF: 0.259

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0721

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.114

Alfa AF: 0.115 Hom.: 279

Bravo AF: 0.115

Asia WGS AF: 0.191 AC: 663 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.2
DANN	Benign	0.80

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: rs1050951; hg19: chr2-143746964; COSMIC: COSV51585354;