15-22935880-T-C

Variant names:

• chr15-22935880-T-C
• rs1822889
• NM_014608.6:c.900+1224A>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.900+1224A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.937 in 152,302 control chromosomes in the GnomAD database, including 66,873 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 0.94 (66873 hom., cov: 33)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.900+1224A>G		intron_variant	Intron 9 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.900+1224A>G		intron_variant	Intron 9 of 30	1	NM_014608.6	ENSP00000481038.1
CYFIP1	ENST00000610365.4	c.900+1224A>G		intron_variant	Intron 10 of 31	1		ENSP00000478779.1
CYFIP1	ENST00000612288.2	c.900+1224A>G		intron_variant	Intron 8 of 29	3		ENSP00000479802.2

Frequencies

GnomAD3 genomes AF: 0.937 AC: 142552 AN: 152184 Hom.: 66806 Cov.: 33

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.882

Gnomad SAS AF: 0.903

Gnomad FIN AF: 0.942

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.938

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

GnomAD4 genome AF: 0.937 AC: 142678 AN: 152302 Hom.: 66873 Cov.: 33 AF XY: 0.936 AC XY: 69700 AN XY: 74466

African (AFR) AF: 0.966 AC: 40161 AN: 41574

American (AMR) AF: 0.952 AC: 14558 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.927 AC: 3215 AN: 3470

East Asian (EAS) AF: 0.882 AC: 4578 AN: 5188

South Asian (SAS) AF: 0.902 AC: 4350 AN: 4820

European-Finnish (FIN) AF: 0.942 AC: 9983 AN: 10602

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62702 AN: 68028

Other (OTH) AF: 0.939 AC: 1986 AN: 2116

Alfa AF: 0.932 Hom.: 17167

Bravo AF: 0.940

Asia WGS AF: 0.898 AC: 3122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.053
DANN	Benign	0.61
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: rs1822889; hg19: chr15-22937188;