rs4662304

Variant names:

• chr2-142884081-G-A
• rs4662304
• NM_003937.3:c.-19-1268G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003937.3(KYNU):​c.-19-1268G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 152,052 control chromosomes in the GnomAD database, including 21,415 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 0.52 (21415 hom., cov: 32)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• Publications: 2 publications found

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]

KYNU Gene-Disease associations (from GenCC):

• vertebral, cardiac, renal, and limb defects syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• encephalopathy due to hydroxykynureninuria

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• congenital vertebral-cardiac-renal anomalies syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KYNU	NM_003937.3	c.-19-1268G>A		intron_variant	Intron 1 of 13	ENST00000264170.9	NP_003928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KYNU	ENST00000264170.9	c.-19-1268G>A		intron_variant	Intron 1 of 13	1	NM_003937.3	ENSP00000264170.4

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79559 AN: 151934 Hom.: 21378 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.680

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.524 AC: 79640 AN: 152052 Hom.: 21415 Cov.: 32 AF XY: 0.532 AC XY: 39502 AN XY: 74308

African (AFR) AF: 0.618 AC: 25623 AN: 41456

American (AMR) AF: 0.589 AC: 9009 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2841 AN: 5178

South Asian (SAS) AF: 0.682 AC: 3286 AN: 4818

European-Finnish (FIN) AF: 0.513 AC: 5408 AN: 10546

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30357 AN: 67980

Other (OTH) AF: 0.499 AC: 1054 AN: 2112

Alfa AF: 0.493 Hom.: 2445

Bravo AF: 0.533

Asia WGS AF: 0.640 AC: 2219 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.9
DANN	Benign	0.44
PhyloP100		0.20
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4662304; hg19: chr2-143641650;