chr1-70431500-G-T

Variant names:

• chr1-70431500-G-T
• rs663649
• NM_001902.6:c.725-583G>T

Variant summary

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

The NM_001902.6(CTH):​c.725-583G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,014 control chromosomes in the GnomAD database, including 5,573 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 0.26 (5573 hom., cov: 32)
• Consequence: CTH NM_001902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 12 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

ENSG00000306600 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 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.725-583G>T		intron	N/A	NP_001893.2
	CTH	NM_001190463.2		c.629-583G>T		intron	N/A	NP_001177392.1
	CTH	NM_153742.5		c.593-583G>T		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.725-583G>T		intron	N/A	ENSP00000359976.3
	CTH	ENST00000346806.2	TSL:1	c.593-583G>T		intron	N/A	ENSP00000311554.2
	CTH	ENST00000411986.6	TSL:2	c.629-583G>T		intron	N/A	ENSP00000413407.2

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40240 AN: 151896 Hom.: 5573 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.0612

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.265 AC: 40244 AN: 152014 Hom.: 5573 Cov.: 32 AF XY: 0.263 AC XY: 19555 AN XY: 74310

African (AFR) AF: 0.238 AC: 9848 AN: 41456

American (AMR) AF: 0.208 AC: 3176 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 910 AN: 3470

East Asian (EAS) AF: 0.0608 AC: 315 AN: 5182

South Asian (SAS) AF: 0.198 AC: 954 AN: 4822

European-Finnish (FIN) AF: 0.341 AC: 3597 AN: 10544

Middle Eastern (MID) AF: 0.305 AC: 89 AN: 292

European-Non Finnish (NFE) AF: 0.303 AC: 20607 AN: 67950

Other (OTH) AF: 0.266 AC: 561 AN: 2112

Alfa AF: 0.285 Hom.: 19339

Bravo AF: 0.253

Asia WGS AF: 0.108 AC: 377 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.51
PhyloP100		0.31
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: rs663649; hg19: chr1-70897183;