rs556972913

Variant names:

• chr8-129855736-T-C
• rs556972913
• NM_001353258.2:c.313A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001353258.2(CYRIB):​c.313A>G​(p.Arg105Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000256 in 1,602,770 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R105S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000026 (1 hom.)
• Consequence: CYRIB NM_001353258.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.36
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.023310035).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYRIB	NM_001353258.2	MANE Select	c.313A>G	p.Arg105Gly	missense	Exon 8 of 14	NP_001340187.1	Q9NUQ9-1
	CYRIB	NM_001256763.2		c.313A>G	p.Arg105Gly	missense	Exon 7 of 13	NP_001243692.1	Q9NUQ9-1
	CYRIB	NM_001353242.2		c.313A>G	p.Arg105Gly	missense	Exon 9 of 15	NP_001340171.1	Q9NUQ9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYRIB	ENST00000694912.1	MANE Select	c.313A>G	p.Arg105Gly	missense	Exon 8 of 14	ENSP00000511587.1	Q9NUQ9-1
	CYRIB	ENST00000519540.5	TSL:1	c.313A>G	p.Arg105Gly	missense	Exon 7 of 13	ENSP00000429499.1	Q9NUQ9-1
	CYRIB	ENST00000522746.5	TSL:1	c.313A>G	p.Arg105Gly	missense	Exon 9 of 15	ENSP00000428117.1	Q9NUQ9-1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152196 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000619 AC: 15 AN: 242352 AF XY: 0.0000839

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000262 AC: 38 AN: 1450456 Hom.: 1 Cov.: 30 AF XY: 0.0000416 AC XY: 30 AN XY: 721440

African (AFR) AF: 0.00 AC: 0 AN: 32660

American (AMR) AF: 0.00 AC: 0 AN: 41420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25468

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.000427 AC: 36 AN: 84246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5594

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108304

Other (OTH) AF: 0.0000167 AC: 1 AN: 59868

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152314 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74492

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	0.99
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
PhyloP100		2.4
Sift4G	Benign	0.47	T
Vest4		0.20
MVP		0.49
ClinPred		0.090	T
GERP RS		-0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.26
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs556972913; hg19: chr8-130867982;