15-22869605-G-C

Position:

• chr15-22869605-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.*423C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 154,020 control chromosomes in the GnomAD database, including 1,781 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 0.12 (1772 hom., cov: 33)
  • Exomes 𝑓: 0.057 (9 hom.)
• Consequence: CYFIP1 NM_014608.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.631

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=-0.58).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.*423C>G		3_prime_UTR_variant	31/31	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928	c.*423C>G		3_prime_UTR_variant	31/31	1	NM_014608.6	ENSP00000481038.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17795 AN: 152050 Hom.: 1763 Cov.: 33

Gnomad AFR AF: 0.256

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.0776

Gnomad ASJ AF: 0.0726

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.0280

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0432

Gnomad OTH AF: 0.110

GnomAD4 exome AF: 0.0567 AC: 105 AN: 1852 Hom.: 9 Cov.: 0 AF XY: 0.0754 AC XY: 71 AN XY: 942

Gnomad4 AFR exome AF: 0.267

Gnomad4 AMR exome AF: 0.0294

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.271

Gnomad4 SAS exome AF: 0.0800

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0392

Gnomad4 OTH exome AF: 0.0645

GnomAD4 genome AF: 0.117 AC: 17832 AN: 152168 Hom.: 1772 Cov.: 33 AF XY: 0.117 AC XY: 8718 AN XY: 74398

Gnomad4 AFR AF: 0.256

Gnomad4 AMR AF: 0.0774

Gnomad4 ASJ AF: 0.0726

Gnomad4 EAS AF: 0.285

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0280

Gnomad4 NFE AF: 0.0432

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0743 Hom.: 108

Bravo AF: 0.126

Asia WGS AF: 0.251 AC: 871 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.1
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs7733; hg19: chr15-23003463;