chr15-22918055-A-T

Variant names:

• chr15-22918055-A-T
• rs2289816
• NM_014608.6:c.1527-120T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014608.6(CYFIP1):​c.1527-120T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000986 in 1,014,072 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 9.9e-7 (0 hom.)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014608.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP1	NM_014608.6	MANE Select	c.1527-120T>A		intron	N/A	NP_055423.1
	CYFIP1	NM_001324119.2		c.1629-120T>A		intron	N/A	NP_001311048.1
	CYFIP1	NM_001287810.4		c.1527-120T>A		intron	N/A	NP_001274739.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP1	ENST00000617928.5	TSL:1 MANE Select	c.1527-120T>A		intron	N/A	ENSP00000481038.1
	CYFIP1	ENST00000610365.4	TSL:1	c.1527-120T>A		intron	N/A	ENSP00000478779.1
	CYFIP1	ENST00000900867.1		c.1572-120T>A		intron	N/A	ENSP00000570926.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 9.86e-7 AC: 1 AN: 1014072 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 509132

African (AFR) AF: 0.00 AC: 0 AN: 22210

American (AMR) AF: 0.00 AC: 0 AN: 26254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17426

East Asian (EAS) AF: 0.00 AC: 0 AN: 34672

South Asian (SAS) AF: 0.00 AC: 0 AN: 62906

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46256

Middle Eastern (MID) AF: 0.000224 AC: 1 AN: 4466

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 755486

Other (OTH) AF: 0.00 AC: 0 AN: 44396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.85
DANN	Benign	0.16
PhyloP100		-0.40

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: rs2289816; hg19: chr15-22955013;