rs3751566

Positions:

• chr15-22932398-G-A

Variant summary

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

The NM_014608.6(CYFIP1):​c.993-58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,274,600 control chromosomes in the GnomAD database, including 63,823 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 0.25 (5853 hom., cov: 33)
  • Exomes 𝑓: 0.31 (57970 hom.)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133

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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP1	NM_014608.6	c.993-58C>T		intron_variant		ENST00000617928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP1	ENST00000617928.5	c.993-58C>T		intron_variant		1	NM_014608.6	P1
CYFIP1	ENST00000610365.4	c.993-58C>T		intron_variant		1		P1
CYFIP1	ENST00000612288.2	c.993-58C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38747 AN: 152074 Hom.: 5846 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.312 AC: 350740 AN: 1122410 Hom.: 57970 AF XY: 0.310 AC XY: 171814 AN XY: 554596

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.419

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.0814

Gnomad4 SAS exome AF: 0.177

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.293

GnomAD4 genome AF: 0.255 AC: 38771 AN: 152190 Hom.: 5853 Cov.: 33 AF XY: 0.251 AC XY: 18683 AN XY: 74398

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.120

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.332

Gnomad4 OTH AF: 0.297

Alfa AF: 0.324 Hom.: 11675

Bravo AF: 0.258

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3751566; hg19: chr15-22940670;