rs1861525

Positions:

• chr7-25121983-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.338

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]

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4013 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYCS	NM_018947.6	c.*1718T>C		3_prime_UTR_variant	3/3	ENST00000305786.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYCS	ENST00000305786.7	c.*1718T>C		3_prime_UTR_variant	3/3	1	NM_018947.6	P1

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4013 AN: 126016 Hom.: 71 Cov.: 32

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: 0 AN: 12 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 10

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.0318 AC: 4013 AN: 126080 Hom.: 71 Cov.: 32 AF XY: 0.0302 AC XY: 1850 AN XY: 61164

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0382

Gnomad4 ASJ AF: 0.0666

Gnomad4 EAS AF: 0.000263

Gnomad4 SAS AF: 0.0169

Gnomad4 FIN AF: 0.00929

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.0363

Alfa AF: 0.0404 Hom.: 185

Bravo AF: 0.0274

Asia WGS AF: 0.00809 AC: 29 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
DANN	Benign	0.55

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

LitVar

Other links and lift over

dbSNP: rs1861525; hg19: chr7-25161602;