15-22876855-A-T

Variant names:

• chr15-22876855-A-T
• rs6606816
• NM_014608.6:c.3043-1584T>A

Variant summary

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

The NM_014608.6(CYFIP1):​c.3043-1584T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 151,454 control chromosomes in the GnomAD database, including 43,327 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 0.75 (43327 hom., cov: 30)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187
• 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.3043-1584T>A		intron_variant	Intron 26 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.3043-1584T>A		intron_variant	Intron 26 of 30	1	NM_014608.6	ENSP00000481038.1

Frequencies

GnomAD3 genomes AF: 0.754 AC: 114136 AN: 151338 Hom.: 43305 Cov.: 30

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.854

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.578

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.856

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.754 AC: 114214 AN: 151454 Hom.: 43327 Cov.: 30 AF XY: 0.758 AC XY: 56092 AN XY: 73962

African (AFR) AF: 0.691 AC: 28503 AN: 41264

American (AMR) AF: 0.816 AC: 12449 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2423 AN: 3466

East Asian (EAS) AF: 0.578 AC: 2962 AN: 5124

South Asian (SAS) AF: 0.857 AC: 4120 AN: 4810

European-Finnish (FIN) AF: 0.856 AC: 8905 AN: 10400

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52244 AN: 67834

Other (OTH) AF: 0.766 AC: 1607 AN: 2098

Alfa AF: 0.754 Hom.: 5096

Bravo AF: 0.747

Asia WGS AF: 0.704 AC: 2441 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.85
PhyloP100		0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6606816; hg19: chr15-22996213;