dbSNP rs1861525: CYCS:c.*1718T>C (chr7-25121983-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_018947.6(CYCS):c.*1718T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0318 in 126,080 control chromosomes in the GnomAD database, including 71 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 0.032 ( 71 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CYCS
NM_018947.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.338

Publications

20 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0318 (4013/126080) while in subpopulation NFE AF = 0.0438 (2738/62488). AF 95% confidence interval is 0.0424. There are 71 homozygotes in GnomAd4. There are 1850 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 4013 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYCS	NM_018947.6 link	c.*1718T>C		3_prime_UTR_variant	Exon 3 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.*1718T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_018947.6	ENSP00000307786.2		P99999

Frequencies

GnomAD3 genomes

AF:

0.0318

AC:

4013

AN:

126016

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0118

Gnomad AMI

AF:

0.0278

Gnomad AMR

AF:

0.0382

Gnomad ASJ

AF:

0.0666

Gnomad EAS

AF:

0.000263

Gnomad SAS

AF:

0.0167

Gnomad FIN

AF:

0.00929

Gnomad MID

AF:

0.0310

Gnomad NFE

AF:

0.0438

Gnomad OTH

AF:

0.0366

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0318

AC:

4013

AN:

126080

Hom.:

Cov.:

AF XY:

0.0302

AC XY:

1850

AN XY:

61164

show subpopulations

African (AFR)

AF:

0.0118

AC:

321

AN:

27308

American (AMR)

AF:

0.0382

AC:

490

AN:

12836

Ashkenazi Jewish (ASJ)

AF:

0.0666

AC:

210

AN:

3154

East Asian (EAS)

AF:

0.000263

AC:

AN:

3796

South Asian (SAS)

AF:

0.0169

AC:

AN:

4020

European-Finnish (FIN)

AF:

0.00929

AC:

AN:

9584

Middle Eastern (MID)

AF:

0.0296

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.0438

AC:

2738

AN:

62488

Other (OTH)

AF:

0.0363

AC:

AN:

1762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

185

369

554

738

923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0370

Hom.:

231

Bravo

AF:

0.0274

Asia WGS

AF:

0.00809

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.2

(source)

DANN

Benign

0.55

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over