1-70431500-G-T

Position:

• chr1-70431500-G-T

Variant summary

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

The ENST00000370938.8(CTH):​c.725-583G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 152,014 control chromosomes in the GnomAD database, including 5,573 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 0.26 (5573 hom., cov: 32)
• Consequence: CTH ENST00000370938.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTH	NM_001902.6	c.725-583G>T		intron_variant		ENST00000370938.8	NP_001893.2
CTH	NM_001190463.2	c.629-583G>T		intron_variant			NP_001177392.1
CTH	NM_153742.5	c.593-583G>T		intron_variant			NP_714964.2
CTH	XM_017000416.3	c.155-583G>T		intron_variant			XP_016855905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTH	ENST00000370938.8	c.725-583G>T		intron_variant		1	NM_001902.6	ENSP00000359976	P1
CTH	ENST00000346806.2	c.593-583G>T		intron_variant		1		ENSP00000311554
CTH	ENST00000411986.6	c.629-583G>T		intron_variant		2		ENSP00000413407

Frequencies

GnomAD3 genomes AF: 0.265 AC: 40240 AN: 151896 Hom.: 5573 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.0612

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.265 AC: 40244 AN: 152014 Hom.: 5573 Cov.: 32 AF XY: 0.263 AC XY: 19555 AN XY: 74310

Gnomad4 AFR AF: 0.238

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.0608

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.266

Alfa AF: 0.288 Hom.: 13258

Bravo AF: 0.253

Asia WGS AF: 0.108 AC: 377 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.9
DANN	Benign	0.51

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: rs663649; hg19: chr1-70897183;