chr15-22935880-T-C

Position:

• chr15-22935880-T-C

Variant summary

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

The NM_014608.6(CYFIP1):​c.900+1224A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 152,302 control chromosomes in the GnomAD database, including 66,873 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 0.94 (66873 hom., cov: 33)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.900+1224A>G		intron_variant		ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.900+1224A>G		intron_variant		1	NM_014608.6	ENSP00000481038	P1
CYFIP1	ENST00000610365.4	c.900+1224A>G		intron_variant		1		ENSP00000478779	P1
CYFIP1	ENST00000612288.2	c.900+1224A>G		intron_variant		3		ENSP00000479802

Frequencies

GnomAD3 genomes AF: 0.937 AC: 142552 AN: 152184 Hom.: 66806 Cov.: 33

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.938

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

GnomAD4 genome AF: 0.937 AC: 142678 AN: 152302 Hom.: 66873 Cov.: 33 AF XY: 0.936 AC XY: 69700 AN XY: 74466

Gnomad4 AFR AF: 0.966

Gnomad4 AMR AF: 0.952

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.882

Gnomad4 SAS AF: 0.902

Gnomad4 FIN AF: 0.942

Gnomad4 NFE AF: 0.922

Gnomad4 OTH AF: 0.939

Alfa AF: 0.931 Hom.: 13486

Bravo AF: 0.940

Asia WGS AF: 0.898 AC: 3122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.053
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs1822889; hg19: chr15-22937188;