rs4778298

Positions:

• chr15-22919487-C-A
• chr15-22919487-C-G
• chr15-22919487-C-T

Variant summary

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

The NM_014608.6(CYFIP1):​c.1360-629G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.368 in 151,902 control chromosomes in the GnomAD database, including 10,504 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 0.37 (10504 hom., cov: 32)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP1	NM_014608.6	c.1360-629G>T		intron_variant		ENST00000617928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP1	ENST00000617928.5	c.1360-629G>T		intron_variant		1	NM_014608.6	P1
CYFIP1	ENST00000610365.4	c.1360-629G>T		intron_variant		1		P1
CYFIP1	ENST00000612288.2	c.1360-629G>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.367 AC: 55780 AN: 151784 Hom.: 10494 Cov.: 32

Gnomad AFR AF: 0.356

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.285

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.380

Gnomad OTH AF: 0.386

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

GnomAD4 genome AF: 0.368 AC: 55825 AN: 151902 Hom.: 10504 Cov.: 32 AF XY: 0.367 AC XY: 27252 AN XY: 74218

Gnomad4 AFR AF: 0.356

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.512

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.380

Gnomad4 OTH AF: 0.391

Alfa AF: 0.381 Hom.: 19723

Bravo AF: 0.363

Asia WGS AF: 0.512 AC: 1783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.65
DANN	Benign	0.75

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4778298; hg19: chr15-22953581;