15-22956906-T-C

Position:

• chr15-22956906-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.-6-9615A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 152,170 control chromosomes in the GnomAD database, including 20,600 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 0.50 (20600 hom., cov: 35)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.407

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.-6-9615A>G		intron_variant		ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.-6-9615A>G		intron_variant		1	NM_014608.6	ENSP00000481038	P1

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76008 AN: 152052 Hom.: 20558 Cov.: 35

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.500 AC: 76105 AN: 152170 Hom.: 20600 Cov.: 35 AF XY: 0.498 AC XY: 37058 AN XY: 74394

Gnomad4 AFR AF: 0.718

Gnomad4 AMR AF: 0.467

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.228

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.412

Gnomad4 OTH AF: 0.466

Alfa AF: 0.410 Hom.: 18109

Bravo AF: 0.505

Asia WGS AF: 0.335 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs12907198; hg19: chr15-22916162;