rs1145920

Variant names:

• chr1-70418157-A-G
• rs1145920
• NM_001902.6:c.346+125A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-70418157-A-G
• chr1-70418157-A-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.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 NM_001902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50
• Publications: 14 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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CTH	NM_001902.6	c.346+125A>G		intron_variant	Intron 3 of 11	ENST00000370938.8	NP_001893.2
CTH	NM_001190463.2	c.250+2120A>G		intron_variant	Intron 2 of 10		NP_001177392.1
CTH	NM_153742.5	c.346+125A>G		intron_variant	Intron 3 of 10		NP_714964.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTH	ENST00000370938.8	c.346+125A>G		intron_variant	Intron 3 of 11	1	NM_001902.6	ENSP00000359976.3
CTH	ENST00000346806.2	c.346+125A>G		intron_variant	Intron 3 of 10	1		ENSP00000311554.2
CTH	ENST00000411986.6	c.250+2120A>G		intron_variant	Intron 2 of 10	2		ENSP00000413407.2
CTH	ENST00000464926.1	n.394+2120A>G		intron_variant	Intron 2 of 5	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

African (AFR) AF: 0.794 AC: 18719 AN: 23580

American (AMR) AF: 0.859 AC: 29562 AN: 34408

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 16113 AN: 22242

East Asian (EAS) AF: 0.813 AC: 27379 AN: 33682

South Asian (SAS) AF: 0.793 AC: 55317 AN: 69754

European-Finnish (FIN) AF: 0.738 AC: 30394 AN: 41158

Middle Eastern (MID) AF: 0.741 AC: 2732 AN: 3688

European-Non Finnish (NFE) AF: 0.743 AC: 543588 AN: 731962

Other (OTH) AF: 0.759 AC: 34138 AN: 44998

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

African (AFR) AF: 0.793 AC: 32912 AN: 41492

American (AMR) AF: 0.822 AC: 12561 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 2527 AN: 3466

East Asian (EAS) AF: 0.820 AC: 4244 AN: 5174

South Asian (SAS) AF: 0.799 AC: 3859 AN: 4830

European-Finnish (FIN) AF: 0.738 AC: 7795 AN: 10564

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50260 AN: 67984

Other (OTH) AF: 0.763 AC: 1609 AN: 2108

Alfa AF: 0.751 Hom.: 143009

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
PhyloP100		-2.5
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: rs1145920; hg19: chr1-70883840;