7-25124125-A-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_018947.6(CYCS):c.-6T>G variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 1,611,606 control chromosomes in the GnomAD database, including 2,311 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.040 ( 167 hom., cov: 33)

Exomes 𝑓: 0.050 ( 2144 hom. )

Consequence

CYCS
NM_018947.6 splice_region

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.696

Publications

5 publications found

Variant links:

Genes affected

CYCS (HGNC:19986): (cytochrome c, somatic) This gene encodes a small heme protein that functions as a central component of the electron transport chain in mitochondria. The encoded protein associates with the inner membrane of the mitochondrion where it accepts electrons from cytochrome b and transfers them to the cytochrome oxidase complex. This protein is also involved in initiation of apoptosis. Mutations in this gene are associated with autosomal dominant nonsyndromic thrombocytopenia. Numerous processed pseudogenes of this gene are found throughout the human genome.[provided by RefSeq, Jul 2010]

CYCS Gene-Disease associations (from GenCC):

thrombocytopenia 4
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics
autosomal thrombocytopenia with normal platelets
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

CYCS links:

ENSG00000296268 (HGNC:):

ENSG00000296268 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 7-25124125-A-C is Benign according to our data. Variant chr7-25124125-A-C is described in ClinVar as Benign. ClinVar VariationId is 261063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYCS	NM_018947.6 link	c.-6T>G		splice_region_variant	Exon 2 of 3	ENST00000305786.7	NP_061820.1	P99999G4XXL9
CYCS	NM_018947.6 link	c.-6T>G		5_prime_UTR_variant	Exon 2 of 3	ENST00000305786.7	NP_061820.1	P99999G4XXL9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYCS	ENST00000305786.7 link	c.-6T>G		splice_region_variant	Exon 2 of 3	1	NM_018947.6	ENSP00000307786.2		P99999
CYCS	ENST00000305786.7 link	c.-6T>G		5_prime_UTR_variant	Exon 2 of 3	1	NM_018947.6	ENSP00000307786.2		P99999

Frequencies

GnomAD3 genomes

AF:

0.0400

AC:

6084

AN:

152090

Hom.:

167

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0109

Gnomad AMI

AF:

0.0758

Gnomad AMR

AF:

0.0257

Gnomad ASJ

AF:

0.00865

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00477

Gnomad FIN

AF:

0.0960

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0595

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.0399

AC:

9888

AN:

247572

AF XY:

0.0399

show subpopulations

Gnomad AFR exome

AF:

0.00937

Gnomad AMR exome

AF:

0.0163

Gnomad ASJ exome

AF:

0.00749

Gnomad EAS exome

AF:

0.000218

Gnomad FIN exome

AF:

0.0905

Gnomad NFE exome

AF:

0.0602

Gnomad OTH exome

AF:

0.0360

GnomAD4 exome

AF:

0.0499

AC:

72870

AN:

1459398

Hom.:

2144

Cov.:

AF XY:

0.0488

AC XY:

35404

AN XY:

726172

show subpopulations

African (AFR)

AF:

0.00753

AC:

252

AN:

33458

American (AMR)

AF:

0.0169

AC:

755

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00853

AC:

223

AN:

26128

East Asian (EAS)

AF:

0.000101

AC:

AN:

39696

South Asian (SAS)

AF:

0.00808

AC:

697

AN:

86230

European-Finnish (FIN)

AF:

0.0895

AC:

4659

AN:

52060

Middle Eastern (MID)

AF:

0.00399

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0574

AC:

63771

AN:

1111012

Other (OTH)

AF:

0.0412

AC:

2486

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

3119

6238

9356

12475

15594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2214

4428

6642

8856

11070

<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:

0.0400

AC:

6085

AN:

152208

Hom.:

167

Cov.:

AF XY:

0.0404

AC XY:

3007

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0109

AC:

452

AN:

41530

American (AMR)

AF:

0.0257

AC:

393

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00865

AC:

AN:

3468

East Asian (EAS)

AF:

0.000385

AC:

AN:

5190

South Asian (SAS)

AF:

0.00477

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0960

AC:

1016

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0595

AC:

4046

AN:

68016

Other (OTH)

AF:

0.0255

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

292

585

877

1170

1462

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0431

Hom.:

193

Bravo

AF:

0.0327

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0500

EpiControl

AF:

0.0468

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Thrombocytopenia 4

Benign:1

Nov 22, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.28

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.28

Position offset: -1

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over