rs4778298

Variant names:

• chr15-22919487-C-A
• rs4778298
• NM_014608.6:c.1360-629G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.1360-629G>T		intron_variant	Intron 13 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.1360-629G>T		intron_variant	Intron 13 of 30	1	NM_014608.6	ENSP00000481038.1
CYFIP1	ENST00000610365.4	c.1360-629G>T		intron_variant	Intron 14 of 31	1		ENSP00000478779.1
CYFIP1	ENST00000612288.2	c.1360-629G>T		intron_variant	Intron 12 of 29	3		ENSP00000479802.2

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

African (AFR) AF: 0.356 AC: 14739 AN: 41378

American (AMR) AF: 0.284 AC: 4347 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1455 AN: 3470

East Asian (EAS) AF: 0.503 AC: 2598 AN: 5170

South Asian (SAS) AF: 0.512 AC: 2468 AN: 4820

European-Finnish (FIN) AF: 0.300 AC: 3164 AN: 10538

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.380 AC: 25791 AN: 67950

Other (OTH) AF: 0.391 AC: 821 AN: 2098

Alfa AF: 0.377 Hom.: 30496

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
PhyloP100		-0.30

Splicing

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

Other links and lift over

dbSNP: rs4778298; hg19: chr15-22953581;