rs681475

Positions:

• chr1-70415034-T-C

Variant summary

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

The NM_001902.6(CTH):​c.169-922T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.642 in 151,974 control chromosomes in the GnomAD database, including 31,547 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 0.64 (31547 hom., cov: 31)
• Consequence: CTH NM_001902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CTH	NM_001902.6	c.169-922T>C		intron_variant		ENST00000370938.8
CTH	NM_001190463.2	c.169-922T>C		intron_variant
CTH	NM_153742.5	c.169-922T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTH	ENST00000370938.8	c.169-922T>C		intron_variant		1	NM_001902.6	P1
CTH	ENST00000346806.2	c.169-922T>C		intron_variant		1
CTH	ENST00000411986.6	c.169-922T>C		intron_variant		2
CTH	ENST00000464926.1	n.313-922T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97478 AN: 151856 Hom.: 31527 Cov.: 31

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.519

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.642 AC: 97532 AN: 151974 Hom.: 31547 Cov.: 31 AF XY: 0.640 AC XY: 47538 AN XY: 74284

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.651

Gnomad4 ASJ AF: 0.668

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.628

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.633

Alfa AF: 0.668 Hom.: 44961

Bravo AF: 0.642

Asia WGS AF: 0.533 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.76

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: rs681475; hg19: chr1-70880717;