Variant 7-25124125-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
CYCS	NM_018947.6 link	c.-6T>G		splice_region_variant	2/3	ENST00000305786.7	NP_061820.1	P99999G4XXL9
CYCS	NM_018947.6 link	c.-6T>G		5_prime_UTR_variant	2/3	ENST00000305786.7	NP_061820.1	P99999G4XXL9

Ensembl

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

GnomAD3 exomes

AF:

0.0399

AC:

9888

AN:

247572

Hom.:

309

AF XY:

0.0399

AC XY:

5377

AN XY:

134612

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 SAS exome

AF:

0.00821

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

Gnomad4 AFR exome

AF:

0.00753

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.00853

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00808

Gnomad4 FIN exome

AF:

0.0895

Gnomad4 NFE exome

AF:

0.0574

Gnomad4 OTH exome

AF:

0.0412

GnomAD4 genome

AF:

0.0400

AC:

6085

AN:

152208

Hom.:

167

Cov.:

AF XY:

0.0404

AC XY:

3007

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0109

Gnomad4 AMR

AF:

0.0257

Gnomad4 ASJ

AF:

0.00865

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00477

Gnomad4 FIN

AF:

0.0960

Gnomad4 NFE

AF:

0.0595

Gnomad4 OTH

AF:

0.0255

Alfa

AF:

0.0478

Hom.:

124

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

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Thrombocytopenia 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.85

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over