rs17137196

Variant names:

• chr15-22910103-G-C
• rs17137196
• NM_014608.6:c.2268+417C>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.2268+417C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 152,252 control chromosomes in the GnomAD database, including 513 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 0.068 (513 hom., cov: 33)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.804
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.2268+417C>G		intron_variant	Intron 20 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.2268+417C>G		intron_variant	Intron 20 of 30	1	NM_014608.6	ENSP00000481038.1

Frequencies

GnomAD3 genomes AF: 0.0683 AC: 10394 AN: 152134 Hom.: 514 Cov.: 33

Gnomad AFR AF: 0.0205

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0700

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0264

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0837

Gnomad OTH AF: 0.0863

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

GnomAD4 genome AF: 0.0682 AC: 10388 AN: 152252 Hom.: 513 Cov.: 33 AF XY: 0.0686 AC XY: 5103 AN XY: 74438

African (AFR) AF: 0.0204 AC: 850 AN: 41568

American (AMR) AF: 0.120 AC: 1839 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0700 AC: 243 AN: 3470

East Asian (EAS) AF: 0.120 AC: 624 AN: 5186

South Asian (SAS) AF: 0.123 AC: 593 AN: 4822

European-Finnish (FIN) AF: 0.0264 AC: 280 AN: 10610

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0837 AC: 5693 AN: 67994

Other (OTH) AF: 0.0854 AC: 180 AN: 2108

Alfa AF: 0.0619 Hom.: 50

Bravo AF: 0.0730

Asia WGS AF: 0.125 AC: 434 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.2
DANN	Benign	0.43
PhyloP100		0.80

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: rs17137196; hg19: chr15-22962965;