7-25121995-A-ATGTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018947.6(CYCS):c.*1705_*1706insAACA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (12718 hom., cov: 0)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: CYCS NM_018947.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.379

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 -10 ACMG points.

• BP6: Variant 7-25121995-A-ATGTT is Benign according to our data. Variant chr7-25121995-A-ATGTT is described in ClinVar as [Likely_benign]. Clinvar id is 359923.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYCS	NM_018947.6	c.*1705_*1706insAACA		3_prime_UTR_variant	3/3	ENST00000305786.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYCS	ENST00000305786.7	c.*1705_*1706insAACA		3_prime_UTR_variant	3/3	1	NM_018947.6	P1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 59234 AN: 149116 Hom.: 12685 Cov.: 0

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.398 AC: 59322 AN: 149232 Hom.: 12718 Cov.: 0 AF XY: 0.396 AC XY: 28816 AN XY: 72686

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.390

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.346

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.393

Alfa AF: 0.333 Hom.: 906

Asia WGS AF: 0.477 AC: 1660 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Thrombocytopenia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs141609926; hg19: chr7-25161614;