chr15-22979151-G-C

Position:

• chr15-22979151-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• 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/exons	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.-7+1136C>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.-7+1136C>G		intron_variant		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

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.315

Gnomad4 EAS AF: 0.363

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.345

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
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

Publications

LitVar

Other links and lift over

dbSNP: rs8025779; hg19: chr15-22893917;