rs7175101

chr15-22963861-G-Achr15-22963861-G-Cchr15-22963861-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014608.6(CYFIP1):c.-7+16426C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,930 control chromosomes in the GnomAD database, including 21,392 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 (21392 hom., cov: 31)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP1	NM_014608.6	c.-7+16426C>T		intron_variant		ENST00000617928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP1	ENST00000617928.5	c.-7+16426C>T		intron_variant		1	NM_014608.6	P1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79458 AN: 151812 Hom.: 21352 Cov.: 31

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.524 AC: 79549 AN: 151930 Hom.: 21392 Cov.: 31 AF XY: 0.521 AC XY: 38665 AN XY: 74258

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.391

Gnomad4 SAS AF: 0.424

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.507

Gnomad4 OTH AF: 0.514

Alfa AF: 0.502 Hom.: 24030

Bravo AF: 0.518

Asia WGS AF: 0.387 AC: 1349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.35
Dann	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs7175101; hg19: chr15-22909207;