rs199756669

Variant names:

• chr15-22873610-G-A
• rs199756669
• NM_014608.6:c.3330C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_014608.6(CYFIP1):​c.3330C>T​(p.Arg1110Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00014 in 1,614,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00027 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: CYFIP1 NM_014608.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.35
• Publications: 1 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 15-22873610-G-A is Benign according to our data. Variant chr15-22873610-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 730970.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.35 with no splicing effect.

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.3330C>T	p.Arg1110Arg	synonymous	Exon 29 of 31	NP_055423.1	Q7L576-1
	CYFIP1	NM_001324119.2		c.3432C>T	p.Arg1144Arg	synonymous	Exon 29 of 31	NP_001311048.1
	CYFIP1	NM_001287810.4		c.3330C>T	p.Arg1110Arg	synonymous	Exon 30 of 32	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.3330C>T	p.Arg1110Arg	synonymous	Exon 29 of 31	ENSP00000481038.1	Q7L576-1
	CYFIP1	ENST00000610365.4	TSL:1	c.3330C>T	p.Arg1110Arg	synonymous	Exon 30 of 32	ENSP00000478779.1	Q7L576-1
	CYFIP1	ENST00000617556.4	TSL:1	c.2037C>T	p.Arg679Arg	synonymous	Exon 14 of 16	ENSP00000480525.1	Q7L576-2

Frequencies

GnomAD3 genomes AF: 0.000269 AC: 41 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000267 AC: 67 AN: 251362 AF XY: 0.000236

Gnomad AFR exome AF: 0.000554

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00159

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000127 AC: 185 AN: 1461884 Hom.: 0 Cov.: 32 AF XY: 0.000128 AC XY: 93 AN XY: 727246

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.000648 AC: 29 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00161 AC: 42 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000719 AC: 80 AN: 1112002

Other (OTH) AF: 0.000232 AC: 14 AN: 60396

GnomAD4 genome AF: 0.000269 AC: 41 AN: 152360 Hom.: 0 Cov.: 33 AF XY: 0.000228 AC XY: 17 AN XY: 74500

African (AFR) AF: 0.000601 AC: 25 AN: 41590

American (AMR) AF: 0.000327 AC: 5 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000343 Hom.: 0

Bravo AF: 0.000314

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	0.92
DANN	Benign	0.87
PhyloP100		-1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8

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: rs199756669; hg19: chr15-22999458;