rs8028440

Variant names:

• chr15-22952350-G-A
• rs8028440
• NM_014608.6:c.-6-5059C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-22952350-G-A
• chr15-22952350-G-C

Variant summary

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

The NM_014608.6(CYFIP1):​c.-6-5059C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,842 control chromosomes in the GnomAD database, including 5,067 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 0.24 (5067 hom., cov: 31)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.-6-5059C>T		intron_variant	Intron 1 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.-6-5059C>T		intron_variant	Intron 1 of 30	1	NM_014608.6	ENSP00000481038.1

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36713 AN: 151724 Hom.: 5055 Cov.: 31

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.00193

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.250

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.242 AC: 36761 AN: 151842 Hom.: 5067 Cov.: 31 AF XY: 0.238 AC XY: 17686 AN XY: 74214

African (AFR) AF: 0.354 AC: 14629 AN: 41340

American (AMR) AF: 0.170 AC: 2597 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 722 AN: 3466

East Asian (EAS) AF: 0.00194 AC: 10 AN: 5160

South Asian (SAS) AF: 0.125 AC: 603 AN: 4814

European-Finnish (FIN) AF: 0.250 AC: 2637 AN: 10536

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14771 AN: 67954

Other (OTH) AF: 0.235 AC: 494 AN: 2104

Alfa AF: 0.218 Hom.: 1977

Bravo AF: 0.243

Asia WGS AF: 0.0810 AC: 282 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.4
DANN	Benign	0.82
PhyloP100		0.031

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: rs8028440; hg19: chr15-22920718;