8-129968226-C-T

Variant names:

• chr8-129968226-C-T
• rs10092658
• NM_001353258.2:c.-137+2717G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 11 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001353258.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYRIB	NM_001353258.2	MANE Select	c.-137+2717G>A		intron	N/A	NP_001340187.1
	CYRIB	NM_001353242.2		c.-243+2717G>A		intron	N/A	NP_001340171.1
	CYRIB	NM_001353243.2		c.-233+2717G>A		intron	N/A	NP_001340172.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYRIB	ENST00000694912.1	MANE Select	c.-137+2717G>A		intron	N/A	ENSP00000511587.1
	CYRIB	ENST00000523509.5	TSL:1	c.-233+2717G>A		intron	N/A	ENSP00000429802.1
	CYRIB	ENST00000401979.6	TSL:2	c.-243+2717G>A		intron	N/A	ENSP00000384880.2

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

African (AFR) AF: 0.0319 AC: 1327 AN: 41558

American (AMR) AF: 0.0419 AC: 641 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5180

South Asian (SAS) AF: 0.0481 AC: 232 AN: 4824

European-Finnish (FIN) AF: 0.0522 AC: 553 AN: 10590

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0589 AC: 4006 AN: 68030

Other (OTH) AF: 0.0615 AC: 130 AN: 2114

Alfa AF: 0.0546 Hom.: 1031

Bravo AF: 0.0445

Asia WGS AF: 0.0230 AC: 78 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	4.1
DANN	Benign	0.57
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs10092658; hg19: chr8-130980472;