8-129968226-C-T

Position:

• chr8-129968226-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001353258.2(CYRIB):​c.-137+2717G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,272 control chromosomes in the GnomAD database, including 170 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 0.046 (170 hom., cov: 32)
• Consequence: CYRIB NM_001353258.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.924

Genes affected

CYRIB (HGNC:25216): (CYFIP related Rac1 interactor B) Enables small GTPase binding activity. Involved in several processes, including cellular response to molecule of bacterial origin; negative regulation of small GTPase mediated signal transduction; and regulation of organelle organization. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYRIB	NM_001353258.2	c.-137+2717G>A		intron_variant		ENST00000694912.1	NP_001340187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYRIB	ENST00000694912.1	c.-137+2717G>A		intron_variant			NM_001353258.2	ENSP00000511587	P4

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7070 AN: 152154 Hom.: 171 Cov.: 32

Gnomad AFR AF: 0.0320

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0420

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0522

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0589

Gnomad OTH AF: 0.0626

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0464 AC: 7068 AN: 152272 Hom.: 170 Cov.: 32 AF XY: 0.0459 AC XY: 3415 AN XY: 74440

Gnomad4 AFR AF: 0.0319

Gnomad4 AMR AF: 0.0419

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.0481

Gnomad4 FIN AF: 0.0522

Gnomad4 NFE AF: 0.0589

Gnomad4 OTH AF: 0.0615

Alfa AF: 0.0557 Hom.: 547

Bravo AF: 0.0445

Asia WGS AF: 0.0230 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.1
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10092658; hg19: chr8-130980472;