rs3751566

Variant names:

• chr15-22932398-G-A
• rs3751566
• NM_014608.6:c.993-58C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-22932398-G-A
• chr15-22932398-G-C
• chr15-22932398-G-T

Variant summary

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

The NM_014608.6(CYFIP1):​c.993-58C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.306 in 1,274,600 control chromosomes in the GnomAD database, including 63,823 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 0.25 (5853 hom., cov: 33)
  • Exomes 𝑓: 0.31 (57970 hom.)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.133
• Publications: 12 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014608.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP1	NM_014608.6	MANE Select	c.993-58C>T		intron	N/A	NP_055423.1	Q7L576-1
	CYFIP1	NM_001324119.2		c.1095-58C>T		intron	N/A	NP_001311048.1
	CYFIP1	NM_001287810.4		c.993-58C>T		intron	N/A	NP_001274739.1	Q7L576-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP1	ENST00000617928.5	TSL:1 MANE Select	c.993-58C>T		intron	N/A	ENSP00000481038.1	Q7L576-1
	CYFIP1	ENST00000610365.4	TSL:1	c.993-58C>T		intron	N/A	ENSP00000478779.1	Q7L576-1
	CYFIP1	ENST00000900867.1		c.993-58C>T		intron	N/A	ENSP00000570926.1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38747 AN: 152074 Hom.: 5846 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.332

Gnomad OTH AF: 0.295

GnomAD4 exome AF: 0.312 AC: 350740 AN: 1122410 Hom.: 57970 AF XY: 0.310 AC XY: 171814 AN XY: 554596

African (AFR) AF: 0.104 AC: 2577 AN: 24670

American (AMR) AF: 0.419 AC: 9483 AN: 22616

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 5039 AN: 19406

East Asian (EAS) AF: 0.0814 AC: 2623 AN: 32214

South Asian (SAS) AF: 0.177 AC: 11021 AN: 62192

European-Finnish (FIN) AF: 0.299 AC: 14047 AN: 47046

Middle Eastern (MID) AF: 0.317 AC: 1519 AN: 4798

European-Non Finnish (NFE) AF: 0.337 AC: 290310 AN: 861284

Other (OTH) AF: 0.293 AC: 14121 AN: 48184

GnomAD4 genome AF: 0.255 AC: 38771 AN: 152190 Hom.: 5853 Cov.: 33 AF XY: 0.251 AC XY: 18683 AN XY: 74398

African (AFR) AF: 0.110 AC: 4579 AN: 41532

American (AMR) AF: 0.349 AC: 5334 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3470

East Asian (EAS) AF: 0.120 AC: 623 AN: 5188

South Asian (SAS) AF: 0.154 AC: 745 AN: 4824

European-Finnish (FIN) AF: 0.290 AC: 3066 AN: 10580

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.332 AC: 22561 AN: 67978

Other (OTH) AF: 0.297 AC: 628 AN: 2112

Alfa AF: 0.320 Hom.: 15718

Bravo AF: 0.258

Asia WGS AF: 0.126 AC: 439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.7
DANN	Benign	0.78
PhyloP100		0.13

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3751566; hg19: chr15-22940670;