15-22955472-T-C

Position:

• chr15-22955472-T-C

Variant summary

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

The NM_014608.6(CYFIP1):​c.-6-8181A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 152,134 control chromosomes in the GnomAD database, including 35,155 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 0.68 (35155 hom., cov: 33)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP1	NM_014608.6	c.-6-8181A>G		intron_variant		ENST00000617928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP1	ENST00000617928.5	c.-6-8181A>G		intron_variant		1	NM_014608.6	P1

Frequencies

GnomAD3 genomes AF: 0.678 AC: 103050 AN: 152014 Hom.: 35117 Cov.: 33

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.658

Gnomad OTH AF: 0.707

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.678 AC: 103137 AN: 152134 Hom.: 35155 Cov.: 33 AF XY: 0.679 AC XY: 50505 AN XY: 74380

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.704

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.811

Gnomad4 SAS AF: 0.660

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.658

Gnomad4 OTH AF: 0.706

Alfa AF: 0.659 Hom.: 4194

Bravo AF: 0.690

Asia WGS AF: 0.743 AC: 2581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.051
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6606803; hg19: chr15-22917596;