chr1-70438385-A-G

Variant names:

• chr1-70438385-A-G
• rs515064
• NM_001902.6:c.1053-303A>G

Variant summary

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

The NM_001902.6(CTH):​c.1053-303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.334 in 152,052 control chromosomes in the GnomAD database, including 8,659 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 0.33 (8659 hom., cov: 32)
• Consequence: CTH NM_001902.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 7 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

ENSG00000306600 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTH	NM_001902.6	c.1053-303A>G		intron_variant	Intron 10 of 11	ENST00000370938.8	NP_001893.2
CTH	NM_001190463.2	c.957-303A>G		intron_variant	Intron 9 of 10		NP_001177392.1
CTH	NM_153742.5	c.921-303A>G		intron_variant	Intron 9 of 10		NP_714964.2
CTH	XM_017000416.3	c.483-303A>G		intron_variant	Intron 7 of 8		XP_016855905.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTH	ENST00000370938.8	c.1053-303A>G		intron_variant	Intron 10 of 11	1	NM_001902.6	ENSP00000359976.3

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50769 AN: 151934 Hom.: 8656 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.243

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.334 AC: 50787 AN: 152052 Hom.: 8659 Cov.: 32 AF XY: 0.332 AC XY: 24691 AN XY: 74344

African (AFR) AF: 0.377 AC: 15618 AN: 41456

American (AMR) AF: 0.256 AC: 3913 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1138 AN: 3466

East Asian (EAS) AF: 0.236 AC: 1222 AN: 5178

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4826

European-Finnish (FIN) AF: 0.356 AC: 3758 AN: 10560

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22870 AN: 67962

Other (OTH) AF: 0.329 AC: 693 AN: 2108

Alfa AF: 0.331 Hom.: 4521

Bravo AF: 0.327

Asia WGS AF: 0.203 AC: 705 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	0.059
DANN	Benign	0.44
PhyloP100		-1.4
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: rs515064; hg19: chr1-70904068;