15-22914964-T-C

Variant names:

• chr15-22914964-T-C
• rs4134803
• NM_014608.6:c.1829-82A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014608.6(CYFIP1):​c.1829-82A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.367 in 1,426,870 control chromosomes in the GnomAD database, including 99,406 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 0.43 (15089 hom., cov: 31)
  • Exomes 𝑓: 0.36 (84317 hom.)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.1829-82A>G		intron_variant	Intron 16 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.1829-82A>G		intron_variant	Intron 16 of 30	1	NM_014608.6	ENSP00000481038.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65398 AN: 151554 Hom.: 15049 Cov.: 31

Gnomad AFR AF: 0.585

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.359 AC: 457488 AN: 1275202 Hom.: 84317 Cov.: 18 AF XY: 0.357 AC XY: 223893 AN XY: 626624

Gnomad4 AFR exome AF: 0.590

Gnomad4 AMR exome AF: 0.532

Gnomad4 ASJ exome AF: 0.396

Gnomad4 EAS exome AF: 0.498

Gnomad4 SAS exome AF: 0.356

Gnomad4 FIN exome AF: 0.343

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.370

GnomAD4 genome AF: 0.432 AC: 65488 AN: 151668 Hom.: 15089 Cov.: 31 AF XY: 0.431 AC XY: 31904 AN XY: 74076

Gnomad4 AFR AF: 0.585

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.388

Alfa AF: 0.362 Hom.: 20318

Bravo AF: 0.449

Asia WGS AF: 0.402 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.044
DANN	Benign	0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4134803; hg19: chr15-22958104;