chr8-130012788-C-T

Variant names:

• chr8-130012788-C-T
• rs2060983
• NM_001353258.2:c.-190+3582G>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.-190+3582G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,990 control chromosomes in the GnomAD database, including 15,259 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 0.44 (15259 hom., cov: 32)
• Consequence: CYRIB NM_001353258.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYRIB	NM_001353258.2	c.-190+3582G>A		intron_variant	Intron 1 of 13	ENST00000694912.1	NP_001340187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYRIB	ENST00000694912.1	c.-190+3582G>A		intron_variant	Intron 1 of 13		NM_001353258.2	ENSP00000511587.1

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67365 AN: 151874 Hom.: 15231 Cov.: 32

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.400

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.444 AC: 67432 AN: 151990 Hom.: 15259 Cov.: 32 AF XY: 0.444 AC XY: 32999 AN XY: 74278

African (AFR) AF: 0.505 AC: 20933 AN: 41430

American (AMR) AF: 0.461 AC: 7046 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1796 AN: 3472

East Asian (EAS) AF: 0.589 AC: 3041 AN: 5164

South Asian (SAS) AF: 0.556 AC: 2675 AN: 4814

European-Finnish (FIN) AF: 0.307 AC: 3245 AN: 10556

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.400 AC: 27208 AN: 67964

Other (OTH) AF: 0.453 AC: 955 AN: 2108

Alfa AF: 0.419 Hom.: 26526

Bravo AF: 0.456

Asia WGS AF: 0.506 AC: 1762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.86
DANN	Benign	0.56
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2060983; hg19: chr8-131025034;