rs672203

chr1-70421416-A-G

Variant summary

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

The NM_001902.6(CTH):c.347-150A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 795,714 control chromosomes in the GnomAD database, including 47,884 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 0.35 (9370 hom., cov: 32)
  • Exomes 𝑓: 0.34 (38514 hom.)
• Consequence: CTH NM_001902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTH	NM_001902.6	c.347-150A>G		intron_variant		ENST00000370938.8
CTH	NM_001190463.2	c.251-150A>G		intron_variant
CTH	NM_153742.5	c.347-150A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTH	ENST00000370938.8	c.347-150A>G		intron_variant		1	NM_001902.6	P1
CTH	ENST00000346806.2	c.347-150A>G		intron_variant		1
CTH	ENST00000411986.6	c.251-150A>G		intron_variant		2
CTH	ENST00000464926.1	n.395-150A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52770 AN: 151942 Hom.: 9367 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.350

GnomAD4 exome AF: 0.340 AC: 219118 AN: 643654 Hom.: 38514 AF XY: 0.340 AC XY: 115360 AN XY: 339654

Gnomad4 AFR exome AF: 0.339

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.354

Gnomad4 EAS exome AF: 0.234

Gnomad4 SAS exome AF: 0.267

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.363

Gnomad4 OTH exome AF: 0.342

GnomAD4 genome AF: 0.347 AC: 52785 AN: 152060 Hom.: 9370 Cov.: 32 AF XY: 0.344 AC XY: 25595 AN XY: 74332

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.266

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.347

Alfa AF: 0.362 Hom.: 12425

Bravo AF: 0.336

Asia WGS AF: 0.207 AC: 716 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	9.8
Dann	Benign	0.60

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: rs672203; hg19: chr1-70887099; COSMIC: COSV61009775;