15-22942060-T-C

Variant names:

• chr15-22942060-T-C
• rs7403800
• NM_014608.6:c.569+1113A>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.569+1113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,078 control chromosomes in the GnomAD database, including 4,315 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 0.22 (4315 hom., cov: 32)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.569+1113A>G		intron_variant	Intron 6 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.569+1113A>G		intron_variant	Intron 6 of 30	1	NM_014608.6	ENSP00000481038.1
CYFIP1	ENST00000610365.4	c.569+1113A>G		intron_variant	Intron 7 of 31	1		ENSP00000478779.1
CYFIP1	ENST00000612288.2	c.569+1113A>G		intron_variant	Intron 5 of 29	3		ENSP00000479802.2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33616 AN: 151960 Hom.: 4305 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.221 AC: 33656 AN: 152078 Hom.: 4315 Cov.: 32 AF XY: 0.218 AC XY: 16195 AN XY: 74370

African (AFR) AF: 0.336 AC: 13951 AN: 41462

American (AMR) AF: 0.158 AC: 2422 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 647 AN: 3470

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5174

South Asian (SAS) AF: 0.105 AC: 505 AN: 4820

European-Finnish (FIN) AF: 0.232 AC: 2459 AN: 10582

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13036 AN: 67960

Other (OTH) AF: 0.214 AC: 453 AN: 2114

Alfa AF: 0.195 Hom.: 1557

Bravo AF: 0.223

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.83
PhyloP100		-0.093

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: rs7403800; hg19: chr15-22931008;