NM_001353258.2:c.-137+24238C>T

Variant names:

• chr8-129946705-G-A
• rs16904179
• NM_001353258.2:c.-137+24238C>T

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+24238C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0671 in 152,164 control chromosomes in the GnomAD database, including 530 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 0.067 (530 hom., cov: 32)
• Consequence: CYRIB NM_001353258.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.68
• Publications: 6 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]

ENSG00000253720 (HGNC:58396):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 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+24238C>T		intron	N/A	NP_001340187.1
	CYRIB	NM_001353242.2		c.-243+24238C>T		intron	N/A	NP_001340171.1
	CYRIB	NM_001353243.2		c.-233+24238C>T		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+24238C>T		intron	N/A	ENSP00000511587.1
	CYRIB	ENST00000523509.5	TSL:1	c.-233+24238C>T		intron	N/A	ENSP00000429802.1
	CYRIB	ENST00000401979.6	TSL:2	c.-243+24238C>T		intron	N/A	ENSP00000384880.2

Frequencies

GnomAD3 genomes AF: 0.0671 AC: 10198 AN: 152046 Hom.: 527 Cov.: 32

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0729

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0486

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0670

Gnomad OTH AF: 0.0666

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

GnomAD4 genome AF: 0.0671 AC: 10203 AN: 152164 Hom.: 530 Cov.: 32 AF XY: 0.0702 AC XY: 5220 AN XY: 74390

African (AFR) AF: 0.0294 AC: 1221 AN: 41514

American (AMR) AF: 0.0728 AC: 1112 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3472

East Asian (EAS) AF: 0.262 AC: 1356 AN: 5174

South Asian (SAS) AF: 0.209 AC: 1006 AN: 4814

European-Finnish (FIN) AF: 0.0486 AC: 514 AN: 10576

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0670 AC: 4556 AN: 68014

Other (OTH) AF: 0.0673 AC: 142 AN: 2110

Alfa AF: 0.0635 Hom.: 596

Bravo AF: 0.0639

Asia WGS AF: 0.204 AC: 707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.56
PhyloP100		-1.7
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: rs16904179; hg19: chr8-130958951;