rs10889869

Variant names:

• chr1-70412281-G-A
• rs10889869
• NM_001902.6:c.168+698G>A

Variant summary

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

The NM_001902.6(CTH):​c.168+698G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 152,226 control chromosomes in the GnomAD database, including 431 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 0.062 (431 hom., cov: 33)
• Consequence: CTH NM_001902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.96
• Publications: 14 publications found

Genes affected

CTH (HGNC:2501): (cystathionine gamma-lyase) This gene encodes a cytoplasmic enzyme in the trans-sulfuration pathway that converts cystathione derived from methionine into cysteine. Glutathione synthesis in the liver is dependent upon the availability of cysteine. Mutations in this gene cause cystathioninuria. Alternative splicing of this gene results in three transcript variants encoding different isoforms. [provided by RefSeq, Jun 2010]

CTH Gene-Disease associations (from GenCC):

• cystathioninuria

  Inheritance: AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0951 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001902.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTH	NM_001902.6	MANE Select	c.168+698G>A		intron	N/A	NP_001893.2
	CTH	NM_001190463.2		c.168+698G>A		intron	N/A	NP_001177392.1
	CTH	NM_153742.5		c.168+698G>A		intron	N/A	NP_714964.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTH	ENST00000370938.8	TSL:1 MANE Select	c.168+698G>A		intron	N/A	ENSP00000359976.3
	CTH	ENST00000346806.2	TSL:1	c.168+698G>A		intron	N/A	ENSP00000311554.2
	CTH	ENST00000411986.6	TSL:2	c.168+698G>A		intron	N/A	ENSP00000413407.2

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9520 AN: 152108 Hom.: 430 Cov.: 33

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0629

Gnomad EAS AF: 0.0547

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.0497

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

GnomAD4 genome AF: 0.0625 AC: 9512 AN: 152226 Hom.: 431 Cov.: 33 AF XY: 0.0640 AC XY: 4767 AN XY: 74428

African (AFR) AF: 0.0153 AC: 635 AN: 41556

American (AMR) AF: 0.0439 AC: 671 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0629 AC: 218 AN: 3466

East Asian (EAS) AF: 0.0543 AC: 281 AN: 5176

South Asian (SAS) AF: 0.103 AC: 494 AN: 4818

European-Finnish (FIN) AF: 0.130 AC: 1375 AN: 10584

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0837 AC: 5693 AN: 68020

Other (OTH) AF: 0.0491 AC: 104 AN: 2116

Alfa AF: 0.0731 Hom.: 969

Bravo AF: 0.0526

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.71
PhyloP100		2.0
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: rs10889869; hg19: chr1-70877964;