rs12594495

Variant names:

• chr15-22925064-T-C
• rs12594495
• NM_014608.6:c.1359+918A>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.1359+918A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 152,074 control chromosomes in the GnomAD database, including 5,096 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 (5096 hom., cov: 33)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.1359+918A>G		intron_variant	Intron 13 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.1359+918A>G		intron_variant	Intron 13 of 30	1	NM_014608.6	ENSP00000481038.1
CYFIP1	ENST00000610365.4	c.1359+918A>G		intron_variant	Intron 14 of 31	1		ENSP00000478779.1
CYFIP1	ENST00000612288.2	c.1359+918A>G		intron_variant	Intron 12 of 29	3		ENSP00000479802.2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36612 AN: 151956 Hom.: 5085 Cov.: 33

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.417

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.242

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.230

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

GnomAD4 genome AF: 0.241 AC: 36632 AN: 152074 Hom.: 5096 Cov.: 33 AF XY: 0.246 AC XY: 18278 AN XY: 74328

African (AFR) AF: 0.134 AC: 5545 AN: 41484

American (AMR) AF: 0.418 AC: 6374 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 854 AN: 3468

East Asian (EAS) AF: 0.339 AC: 1750 AN: 5168

South Asian (SAS) AF: 0.241 AC: 1164 AN: 4824

European-Finnish (FIN) AF: 0.258 AC: 2732 AN: 10572

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17388 AN: 67984

Other (OTH) AF: 0.230 AC: 487 AN: 2114

Alfa AF: 0.256 Hom.: 16665

Bravo AF: 0.252

Asia WGS AF: 0.256 AC: 889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.4
DANN	Benign	0.85
PhyloP100		0.21

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: rs12594495; hg19: chr15-22948004;