ENST00000799672.1:n.55C>T

Variant names:

• chr1-70411075-G-A
• rs663465
• ENST00000799672.1:n.55C>T

Variant summary

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

The ENST00000799672.1(ENSG00000304098):​n.55C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 380,816 control chromosomes in the GnomAD database, including 61,017 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 0.57 (24861 hom., cov: 31)
  • Exomes 𝑓: 0.55 (36156 hom.)
• Consequence: ENSG00000304098 ENST00000799672.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 13 publications found

Genes affected

ENSG00000304098 (HGNC:):

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000799672.1. 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.-341G>A		upstream_gene	N/A	NP_001893.2
	CTH	NM_001190463.2		c.-341G>A		upstream_gene	N/A	NP_001177392.1
	CTH	NM_153742.5		c.-341G>A		upstream_gene	N/A	NP_714964.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000304098	ENST00000799672.1		n.55C>T		non_coding_transcript_exon	Exon 1 of 1
	CTH	ENST00000370938.8	TSL:1 MANE Select	c.-341G>A		upstream_gene	N/A	ENSP00000359976.3
	CTH	ENST00000411986.6	TSL:2	c.-341G>A		upstream_gene	N/A	ENSP00000413407.2

Frequencies

GnomAD3 genomes AF: 0.567 AC: 86050 AN: 151868 Hom.: 24856 Cov.: 31

Gnomad AFR AF: 0.531

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.553 AC: 126613 AN: 228830 Hom.: 36156 AF XY: 0.541 AC XY: 67250 AN XY: 124216

African (AFR) AF: 0.519 AC: 3348 AN: 6454

American (AMR) AF: 0.606 AC: 7068 AN: 11656

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 2954 AN: 5608

East Asian (EAS) AF: 0.294 AC: 3024 AN: 10286

South Asian (SAS) AF: 0.439 AC: 18330 AN: 41732

European-Finnish (FIN) AF: 0.634 AC: 6541 AN: 10320

Middle Eastern (MID) AF: 0.473 AC: 389 AN: 822

European-Non Finnish (NFE) AF: 0.601 AC: 78348 AN: 130258

Other (OTH) AF: 0.565 AC: 6611 AN: 11694

GnomAD4 genome AF: 0.566 AC: 86088 AN: 151986 Hom.: 24861 Cov.: 31 AF XY: 0.565 AC XY: 41951 AN XY: 74276

African (AFR) AF: 0.531 AC: 22026 AN: 41466

American (AMR) AF: 0.581 AC: 8879 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1920 AN: 3470

East Asian (EAS) AF: 0.307 AC: 1578 AN: 5140

South Asian (SAS) AF: 0.435 AC: 2095 AN: 4812

European-Finnish (FIN) AF: 0.641 AC: 6768 AN: 10564

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40971 AN: 67936

Other (OTH) AF: 0.535 AC: 1132 AN: 2116

Alfa AF: 0.498 Hom.: 1898

Bravo AF: 0.563

Asia WGS AF: 0.377 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.0
DANN	Benign	0.80
PhyloP100		-1.1
PromoterAI		0.095	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs663465; hg19: chr1-70876758;