rs2289816

Variant names:

• chr15-22918055-A-C
• rs2289816
• NM_014608.6:c.1527-120T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-22918055-A-C
• chr15-22918055-A-G
• chr15-22918055-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.1527-120T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 1,164,812 control chromosomes in the GnomAD database, including 378,376 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 0.83 (52165 hom., cov: 32)
  • Exomes 𝑓: 0.80 (326211 hom.)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402
• Publications: 6 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 = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.1527-120T>G		intron_variant	Intron 14 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.1527-120T>G		intron_variant	Intron 14 of 30	1	NM_014608.6	ENSP00000481038.1
CYFIP1	ENST00000610365.4	c.1527-120T>G		intron_variant	Intron 15 of 31	1		ENSP00000478779.1
CYFIP1	ENST00000612288.2	c.1527-120T>G		intron_variant	Intron 13 of 29	3		ENSP00000479802.2
CYFIP1	ENST00000622576.1	n.-148T>G		upstream_gene_variant		4		ENSP00000482459.1

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125633 AN: 152000 Hom.: 52111 Cov.: 32

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.723

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.847

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.833

GnomAD4 exome AF: 0.802 AC: 811795 AN: 1012694 Hom.: 326211 AF XY: 0.805 AC XY: 409078 AN XY: 508468

African (AFR) AF: 0.917 AC: 20348 AN: 22192

American (AMR) AF: 0.807 AC: 21169 AN: 26230

Ashkenazi Jewish (ASJ) AF: 0.837 AC: 14566 AN: 17410

East Asian (EAS) AF: 0.732 AC: 25362 AN: 34644

South Asian (SAS) AF: 0.877 AC: 55132 AN: 62878

European-Finnish (FIN) AF: 0.794 AC: 36712 AN: 46232

Middle Eastern (MID) AF: 0.872 AC: 3896 AN: 4466

European-Non Finnish (NFE) AF: 0.793 AC: 598463 AN: 754286

Other (OTH) AF: 0.815 AC: 36147 AN: 44356

GnomAD4 genome AF: 0.827 AC: 125745 AN: 152118 Hom.: 52165 Cov.: 32 AF XY: 0.826 AC XY: 61430 AN XY: 74346

African (AFR) AF: 0.911 AC: 37819 AN: 41526

American (AMR) AF: 0.802 AC: 12270 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.847 AC: 2941 AN: 3472

East Asian (EAS) AF: 0.769 AC: 3966 AN: 5154

South Asian (SAS) AF: 0.865 AC: 4169 AN: 4820

European-Finnish (FIN) AF: 0.787 AC: 8332 AN: 10582

Middle Eastern (MID) AF: 0.823 AC: 242 AN: 294

European-Non Finnish (NFE) AF: 0.789 AC: 53599 AN: 67968

Other (OTH) AF: 0.834 AC: 1755 AN: 2104

Alfa AF: 0.800 Hom.: 79663

Bravo AF: 0.829

Asia WGS AF: 0.846 AC: 2943 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	0.98
DANN	Benign	0.44
PhyloP100		-0.40

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: rs2289816; hg19: chr15-22955013;