rs7170637

Positions:

• chr15-22903836-C-T

Variant summary

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

The NM_014608.6(CYFIP1):​c.2458G>A​(p.Gly820Ser) variant causes a missense change. The variant allele was found at a frequency of 0.179 in 1,613,908 control chromosomes in the GnomAD database, including 35,131 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G820D) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.29 (9387 hom., cov: 33)
  • Exomes 𝑓: 0.17 (25744 hom.)
• Consequence: CYFIP1 NM_014608.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.04

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 (MetaRNN=0.0048214793).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP1	NM_014608.6	c.2458G>A	p.Gly820Ser	missense_variant	22/31	ENST00000617928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP1	ENST00000617928.5	c.2458G>A	p.Gly820Ser	missense_variant	22/31	1	NM_014608.6	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43334 AN: 152008 Hom.: 9365 Cov.: 33

Gnomad AFR AF: 0.609

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.265

GnomAD3 exomes AF: 0.177 AC: 44486 AN: 251312 Hom.: 6109 AF XY: 0.171 AC XY: 23268 AN XY: 135862

Gnomad AFR exome AF: 0.615

Gnomad AMR exome AF: 0.0997

Gnomad ASJ exome AF: 0.151

Gnomad EAS exome AF: 0.000761

Gnomad SAS exome AF: 0.131

Gnomad FIN exome AF: 0.236

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.168 AC: 246207 AN: 1461782 Hom.: 25744 Cov.: 32 AF XY: 0.167 AC XY: 121302 AN XY: 727194

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.000453

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.233

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.183

GnomAD4 genome AF: 0.285 AC: 43400 AN: 152126 Hom.: 9387 Cov.: 33 AF XY: 0.279 AC XY: 20745 AN XY: 74374

Gnomad4 AFR AF: 0.609

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.261

Alfa AF: 0.186 Hom.: 6373

Bravo AF: 0.298

Asia WGS AF: 0.0850 AC: 295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_noAF	Pathogenic	0.34
CADD	Benign	19
DANN	Benign	0.73
DEOGEN2	Benign	0.054	T;.;T
LIST_S2	Benign	0.66	.;T;T
MetaRNN	Benign	0.0048	T;T;T
Sift4G	Benign	0.78	T;T;T
Vest4		0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.76

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: rs7170637; hg19: chr15-22969232;