rs7403800

Positions:

• chr15-22942060-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.569+1113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,078 control chromosomes in the GnomAD database, including 4,315 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 0.22 (4315 hom., cov: 32)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP1	NM_014608.6	c.569+1113A>G		intron_variant		ENST00000617928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP1	ENST00000617928.5	c.569+1113A>G		intron_variant		1	NM_014608.6	P1
CYFIP1	ENST00000610365.4	c.569+1113A>G		intron_variant		1		P1
CYFIP1	ENST00000612288.2	c.569+1113A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33616 AN: 151960 Hom.: 4305 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.221 AC: 33656 AN: 152078 Hom.: 4315 Cov.: 32 AF XY: 0.218 AC XY: 16195 AN XY: 74370

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.158

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.214

Alfa AF: 0.196 Hom.: 1409

Bravo AF: 0.223

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.83

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: rs7403800; hg19: chr15-22931008;