rs515064

chr1-70438385-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.1053-303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,052 control chromosomes in the GnomAD database, including 8,659 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 0.33 (8659 hom., cov: 32)
• Consequence: CTH NM_001902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTH	NM_001902.6	c.1053-303A>G		intron_variant		ENST00000370938.8
CTH	NM_001190463.2	c.957-303A>G		intron_variant
CTH	NM_153742.5	c.921-303A>G		intron_variant
CTH	XM_017000416.3	c.483-303A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTH	ENST00000370938.8	c.1053-303A>G		intron_variant		1	NM_001902.6	P1
CTH	ENST00000346806.2	c.921-303A>G		intron_variant		1
CTH	ENST00000411986.6	c.957-303A>G		intron_variant		2
CTH	ENST00000482383.1	n.328-303A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50769 AN: 151934 Hom.: 8656 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.334 AC: 50787 AN: 152052 Hom.: 8659 Cov.: 32 AF XY: 0.332 AC XY: 24691 AN XY: 74344

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.329

Alfa AF: 0.330 Hom.: 4044

Bravo AF: 0.327

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.059
Dann	Benign	0.44

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: rs515064; hg19: chr1-70904068;