dbSNP rs663465: CTH:c.-1-340G>A (chr1-70411075-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000896200.1(CTH):c.-1-340G>A variant causes a intron 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

CTH
ENST00000896200.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

Publications

13 publications found

Variant links:

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: Orphanet, Ambry Genetics, ClinGen

CTH links:

ENSG00000304098 (HGNC:):

ENSG00000304098 links:

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ACMG classification

Classification was made for transcript

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: ENST00000896200.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	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	P32929-3
CTH	NM_153742.5		c.-341G>A	upstream_gene	N/A	NP_714964.2

Ensembl Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein
CTH	ENST00000896200.1	c.-1-340G>A	intron	N/A	ENSP00000566259.1
CTH	ENST00000896201.1	c.-2+48G>A	intron	N/A	ENSP00000566260.1
ENSG00000304098	ENST00000799672.1	n.55C>T	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.567

AC:

86050

AN:

151868

Hom.:

24856

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2696

5393

8089

10786

13482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

412

824

1236

1648

2060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.566

AC:

86088

AN:

151986

Hom.:

24861

Cov.:

AF XY:

0.565

AC XY:

41951

AN XY:

74276

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1886

3772

5659

7545

9431

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.80

PhyloP100

-1.1

PromoterAI

0.095

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over