15-22896157-C-T

Variant names:

• chr15-22896157-C-T
• rs1009153
• NM_014608.6:c.2589-3180G>A

Variant summary

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

The NM_014608.6(CYFIP1):​c.2589-3180G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,812 control chromosomes in the GnomAD database, including 9,703 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 0.34 (9703 hom., cov: 32)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.942

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.2589-3180G>A		intron_variant	Intron 22 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.2589-3180G>A		intron_variant	Intron 22 of 30	1	NM_014608.6	ENSP00000481038.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52171 AN: 151694 Hom.: 9693 Cov.: 32

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.501

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.345

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.344 AC: 52213 AN: 151812 Hom.: 9703 Cov.: 32 AF XY: 0.350 AC XY: 25976 AN XY: 74168

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.563

Gnomad4 SAS AF: 0.341

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.356

Gnomad4 OTH AF: 0.340

Alfa AF: 0.350 Hom.: 10314

Bravo AF: 0.353

Asia WGS AF: 0.425 AC: 1477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.58

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: rs1009153; hg19: chr15-22976911;