rs2289821

Variant names:

• chr15-22926124-A-C
• rs2289821
• NM_014608.6:c.1234-17T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-22926124-A-C
• chr15-22926124-A-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.1234-17T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,613,878 control chromosomes in the GnomAD database, including 1,873 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 0.064 (659 hom., cov: 33)
  • Exomes 𝑓: 0.022 (1214 hom.)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.114
• Publications: 8 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 (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.1234-17T>G		intron_variant	Intron 12 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.1234-17T>G		intron_variant	Intron 12 of 30	1	NM_014608.6	ENSP00000481038.1
CYFIP1	ENST00000610365.4	c.1234-17T>G		intron_variant	Intron 13 of 31	1		ENSP00000478779.1
CYFIP1	ENST00000612288.2	c.1234-17T>G		intron_variant	Intron 11 of 29	3		ENSP00000479802.2

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9766 AN: 152026 Hom.: 659 Cov.: 33

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0869

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.0822

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.00631

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0113

Gnomad OTH AF: 0.0531

GnomAD2 exomes AF: 0.0450 AC: 11295 AN: 251216 AF XY: 0.0416

Gnomad AFR exome AF: 0.169

Gnomad AMR exome AF: 0.0917

Gnomad ASJ exome AF: 0.0140

Gnomad EAS exome AF: 0.0838

Gnomad FIN exome AF: 0.00754

Gnomad NFE exome AF: 0.0117

Gnomad OTH exome AF: 0.0307

GnomAD4 exome AF: 0.0225 AC: 32878 AN: 1461734 Hom.: 1214 Cov.: 31 AF XY: 0.0231 AC XY: 16797 AN XY: 727166

African (AFR) AF: 0.168 AC: 5639 AN: 33470

American (AMR) AF: 0.0922 AC: 4122 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0146 AC: 382 AN: 26134

East Asian (EAS) AF: 0.0842 AC: 3342 AN: 39698

South Asian (SAS) AF: 0.0641 AC: 5528 AN: 86246

European-Finnish (FIN) AF: 0.00948 AC: 506 AN: 53372

Middle Eastern (MID) AF: 0.0212 AC: 122 AN: 5768

European-Non Finnish (NFE) AF: 0.0102 AC: 11326 AN: 1111942

Other (OTH) AF: 0.0316 AC: 1911 AN: 60390

GnomAD4 genome AF: 0.0642 AC: 9774 AN: 152144 Hom.: 659 Cov.: 33 AF XY: 0.0644 AC XY: 4793 AN XY: 74390

African (AFR) AF: 0.161 AC: 6679 AN: 41484

American (AMR) AF: 0.0868 AC: 1327 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3472

East Asian (EAS) AF: 0.0820 AC: 424 AN: 5172

South Asian (SAS) AF: 0.0697 AC: 336 AN: 4818

European-Finnish (FIN) AF: 0.00631 AC: 67 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0113 AC: 767 AN: 67986

Other (OTH) AF: 0.0525 AC: 111 AN: 2114

Alfa AF: 0.0316 Hom.: 424

Bravo AF: 0.0732

Asia WGS AF: 0.0960 AC: 335 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	0.87
DANN	Benign	0.67
PhyloP100		-0.11
PromoterAI		-0.0042	Neutral

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: rs2289821; hg19: chr15-22946944;