rs10889869

Positions:

• chr1-70412281-G-A

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTH	NM_001902.6	c.168+698G>A		intron_variant		ENST00000370938.8	NP_001893.2
CTH	NM_001190463.2	c.168+698G>A		intron_variant			NP_001177392.1
CTH	NM_153742.5	c.168+698G>A		intron_variant			NP_714964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTH	ENST00000370938.8	c.168+698G>A		intron_variant		1	NM_001902.6	ENSP00000359976.3
CTH	ENST00000346806.2	c.168+698G>A		intron_variant		1		ENSP00000311554.2
CTH	ENST00000411986.6	c.168+698G>A		intron_variant		2		ENSP00000413407.2
CTH	ENST00000464926.1	n.312+698G>A		intron_variant		5

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

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.0439

Gnomad4 ASJ AF: 0.0629

Gnomad4 EAS AF: 0.0543

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.130

Gnomad4 NFE AF: 0.0837

Gnomad4 OTH AF: 0.0491

Alfa AF: 0.0753 Hom.: 685

Bravo AF: 0.0526

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Benign	0.71

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: rs10889869; hg19: chr1-70877964;