15-22979151-G-C

Variant names:

• chr15-22979151-G-C
• rs8025779
• NM_014608.6:c.-7+1136C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014608.6(CYFIP1):​c.-7+1136C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 151,956 control chromosomes in the GnomAD database, including 9,238 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 0.35 (9238 hom., cov: 32)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.561
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.-7+1136C>G		intron_variant	Intron 1 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.-7+1136C>G		intron_variant	Intron 1 of 30	1	NM_014608.6	ENSP00000481038.1

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52612 AN: 151838 Hom.: 9227 Cov.: 32

Gnomad AFR AF: 0.378

Gnomad AMI AF: 0.271

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.315

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.346 AC: 52649 AN: 151956 Hom.: 9238 Cov.: 32 AF XY: 0.343 AC XY: 25489 AN XY: 74234

African (AFR) AF: 0.378 AC: 15673 AN: 41430

American (AMR) AF: 0.265 AC: 4043 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.315 AC: 1094 AN: 3472

East Asian (EAS) AF: 0.363 AC: 1873 AN: 5154

South Asian (SAS) AF: 0.229 AC: 1103 AN: 4810

European-Finnish (FIN) AF: 0.350 AC: 3703 AN: 10570

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.355 AC: 24107 AN: 67938

Other (OTH) AF: 0.345 AC: 729 AN: 2110

Alfa AF: 0.233 Hom.: 620

Bravo AF: 0.343

Asia WGS AF: 0.277 AC: 962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.0
DANN	Benign	0.50
PhyloP100		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8025779; hg19: chr15-22893917;