rs2289816

Positions:

• chr15-22918055-A-C
• chr15-22918055-A-G
• chr15-22918055-A-T

Variant summary

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

The NM_014608.6(CYFIP1):​c.1527-120T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 1,164,812 control chromosomes in the GnomAD database, including 378,376 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 0.83 (52165 hom., cov: 32)
  • Exomes 𝑓: 0.80 (326211 hom.)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

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 = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.1527-120T>G		intron_variant		ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.1527-120T>G		intron_variant		1	NM_014608.6	ENSP00000481038	P1
CYFIP1	ENST00000610365.4	c.1527-120T>G		intron_variant		1		ENSP00000478779	P1
CYFIP1	ENST00000612288.2	c.1527-120T>G		intron_variant		3		ENSP00000479802

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125633 AN: 152000 Hom.: 52111 Cov.: 32

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.833

GnomAD4 exome AF: 0.802 AC: 811795 AN: 1012694 Hom.: 326211 AF XY: 0.805 AC XY: 409078 AN XY: 508468

Gnomad4 AFR exome AF: 0.917

Gnomad4 AMR exome AF: 0.807

Gnomad4 ASJ exome AF: 0.837

Gnomad4 EAS exome AF: 0.732

Gnomad4 SAS exome AF: 0.877

Gnomad4 FIN exome AF: 0.794

Gnomad4 NFE exome AF: 0.793

Gnomad4 OTH exome AF: 0.815

GnomAD4 genome AF: 0.827 AC: 125745 AN: 152118 Hom.: 52165 Cov.: 32 AF XY: 0.826 AC XY: 61430 AN XY: 74346

Gnomad4 AFR AF: 0.911

Gnomad4 AMR AF: 0.802

Gnomad4 ASJ AF: 0.847

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.787

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.834

Alfa AF: 0.798 Hom.: 62290

Bravo AF: 0.829

Asia WGS AF: 0.846 AC: 2943 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	0.98
DANN	Benign	0.44

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: rs2289816; hg19: chr15-22955013;