rs17841095

chr15-22900872-A-G

Variant summary

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

The NM_014608.6(CYFIP1):c.2588+2834T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0877 in 152,040 control chromosomes in the GnomAD database, including 671 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 0.088 (671 hom., cov: 29)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651

Genes affected

CYFIP1 (HGNC:13759): (cytoplasmic FMR1 interacting protein 1) This gene encodes a protein that regulates cytoskeletal dynamics and protein translation. The encoded protein is a component of the WAVE regulatory complex (WRC), which promotes actin polymerization. This protein also interacts with the synaptic functional regulator FMR1 protein and translation initiation factor 4E to inhibit protein translation. A large chromosomal deletion including this gene is associated with increased risk of schizophrenia and epilepsy in human patients. Reduced expression of this gene has been observed in various human cancers and the encoded protein may inhibit tumor invasion. [provided by RefSeq, Mar 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP1	NM_014608.6	c.2588+2834T>C		intron_variant		ENST00000617928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP1	ENST00000617928.5	c.2588+2834T>C		intron_variant		1	NM_014608.6	P1

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 13329 AN: 151920 Hom.: 670 Cov.: 29

Gnomad AFR AF: 0.0595

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0981

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0240

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0877 AC: 13337 AN: 152040 Hom.: 671 Cov.: 29 AF XY: 0.0839 AC XY: 6234 AN XY: 74312

Gnomad4 AFR AF: 0.0597

Gnomad4 AMR AF: 0.0979

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0240

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.109

Alfa AF: 0.105 Hom.: 1878

Bravo AF: 0.0917

Asia WGS AF: 0.152 AC: 527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	5.8
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17841095; hg19: chr15-22972196;