rs2028794

Variant names:

• chr15-22953653-A-G
• rs2028794
• NM_014608.6:c.-6-6362T>C

Variant summary

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

The NM_014608.6(CYFIP1):​c.-6-6362T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 152,196 control chromosomes in the GnomAD database, including 4,249 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 0.22 (4249 hom., cov: 33)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.-6-6362T>C		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.-6-6362T>C		intron_variant	Intron 1 of 30	1	NM_014608.6	ENSP00000481038.1

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33758 AN: 152078 Hom.: 4240 Cov.: 33

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.259

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

GnomAD4 genome AF: 0.222 AC: 33784 AN: 152196 Hom.: 4249 Cov.: 33 AF XY: 0.222 AC XY: 16550 AN XY: 74402

African (AFR) AF: 0.108 AC: 4500 AN: 41534

American (AMR) AF: 0.317 AC: 4847 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 656 AN: 3472

East Asian (EAS) AF: 0.247 AC: 1277 AN: 5178

South Asian (SAS) AF: 0.135 AC: 653 AN: 4830

European-Finnish (FIN) AF: 0.271 AC: 2867 AN: 10578

Middle Eastern (MID) AF: 0.338 AC: 98 AN: 290

European-Non Finnish (NFE) AF: 0.267 AC: 18147 AN: 68010

Other (OTH) AF: 0.260 AC: 549 AN: 2108

Alfa AF: 0.252 Hom.: 5162

Bravo AF: 0.228

Asia WGS AF: 0.184 AC: 639 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	0.26
DANN	Benign	0.83
PhyloP100		-1.2

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

Other links and lift over

dbSNP: rs2028794; hg19: chr15-22919415;