rs1145920

Positions:

• chr1-70418157-A-G
• chr1-70418157-A-T

Variant summary

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

The ENST00000370938.8(CTH):​c.346+125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 1,157,582 control chromosomes in the GnomAD database, including 331,197 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 0.77 (44912 hom., cov: 32)
  • Exomes 𝑓: 0.75 (286285 hom.)
• Consequence: CTH ENST00000370938.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

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 (AMR) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTH	NM_001902.6	c.346+125A>G		intron_variant		ENST00000370938.8	NP_001893.2
CTH	NM_001190463.2	c.250+2120A>G		intron_variant			NP_001177392.1
CTH	NM_153742.5	c.346+125A>G		intron_variant			NP_714964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTH	ENST00000370938.8	c.346+125A>G		intron_variant		1	NM_001902.6	ENSP00000359976	P1
CTH	ENST00000346806.2	c.346+125A>G		intron_variant		1		ENSP00000311554
CTH	ENST00000411986.6	c.250+2120A>G		intron_variant		2		ENSP00000413407
CTH	ENST00000464926.1	n.394+2120A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116611 AN: 151992 Hom.: 44862 Cov.: 32

Gnomad AFR AF: 0.793

Gnomad AMI AF: 0.786

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.729

Gnomad EAS AF: 0.820

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.754 AC: 757942 AN: 1005472 Hom.: 286285 AF XY: 0.754 AC XY: 386354 AN XY: 512178

Gnomad4 AFR exome AF: 0.794

Gnomad4 AMR exome AF: 0.859

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.813

Gnomad4 SAS exome AF: 0.793

Gnomad4 FIN exome AF: 0.738

Gnomad4 NFE exome AF: 0.743

Gnomad4 OTH exome AF: 0.759

GnomAD4 genome AF: 0.767 AC: 116717 AN: 152110 Hom.: 44912 Cov.: 32 AF XY: 0.769 AC XY: 57186 AN XY: 74354

Gnomad4 AFR AF: 0.793

Gnomad4 AMR AF: 0.822

Gnomad4 ASJ AF: 0.729

Gnomad4 EAS AF: 0.820

Gnomad4 SAS AF: 0.799

Gnomad4 FIN AF: 0.738

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.763

Alfa AF: 0.744 Hom.: 84597

Bravo AF: 0.776

Asia WGS AF: 0.804 AC: 2797 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	0.021
DANN	Benign	0.66

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: rs1145920; hg19: chr1-70883840;