rs4293342

Variant names:

• chr15-22968756-A-G
• rs4293342
• NM_014608.6:c.-7+11531T>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.-7+11531T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,004 control chromosomes in the GnomAD database, including 21,447 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 0.52 (21447 hom., cov: 33)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.-7+11531T>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.-7+11531T>C		intron_variant	Intron 1 of 30	1	NM_014608.6	ENSP00000481038.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79462 AN: 151888 Hom.: 21405 Cov.: 33

Gnomad AFR AF: 0.639

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.394

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.523 AC: 79553 AN: 152004 Hom.: 21447 Cov.: 33 AF XY: 0.520 AC XY: 38655 AN XY: 74282

African (AFR) AF: 0.640 AC: 26527 AN: 41460

American (AMR) AF: 0.390 AC: 5959 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1694 AN: 3464

East Asian (EAS) AF: 0.394 AC: 2039 AN: 5174

South Asian (SAS) AF: 0.424 AC: 2044 AN: 4820

European-Finnish (FIN) AF: 0.541 AC: 5707 AN: 10556

Middle Eastern (MID) AF: 0.425 AC: 124 AN: 292

European-Non Finnish (NFE) AF: 0.501 AC: 34028 AN: 67954

Other (OTH) AF: 0.512 AC: 1078 AN: 2106

Alfa AF: 0.502 Hom.: 21245

Bravo AF: 0.517

Asia WGS AF: 0.389 AC: 1355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	4.1
DANN	Benign	0.84
PhyloP100		-0.067

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: rs4293342; hg19: chr15-22904312;