rs2289823

Positions:

• chr15-22945116-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.208-177C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,042 control chromosomes in the GnomAD database, including 5,252 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 (5252 hom., cov: 33)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP1	NM_014608.6	c.208-177C>T		intron_variant		ENST00000617928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP1	ENST00000617928.5	c.208-177C>T		intron_variant		1	NM_014608.6	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37537 AN: 151924 Hom.: 5237 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.0989

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.247 AC: 37589 AN: 152042 Hom.: 5252 Cov.: 33 AF XY: 0.246 AC XY: 18255 AN XY: 74306

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.0991

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.196

Gnomad4 OTH AF: 0.236

Alfa AF: 0.202 Hom.: 5804

Bravo AF: 0.252

Asia WGS AF: 0.143 AC: 496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.15
DANN	Benign	0.70

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: rs2289823; hg19: chr15-22927952;