15-22956906-T-C

Variant names:

• chr15-22956906-T-C
• rs12907198
• NM_014608.6:c.-6-9615A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014608.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP1	NM_014608.6	MANE Select	c.-6-9615A>G		intron	N/A	NP_055423.1
	CYFIP1	NM_001324119.2		c.97-9615A>G		intron	N/A	NP_001311048.1
	CYFIP1	NM_001287810.4		c.-125-8877A>G		intron	N/A	NP_001274739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP1	ENST00000617928.5	TSL:1 MANE Select	c.-6-9615A>G		intron	N/A	ENSP00000481038.1
	CYFIP1	ENST00000610365.4	TSL:1	c.-125-8877A>G		intron	N/A	ENSP00000478779.1
	CYFIP1	ENST00000613006.4	TSL:4	c.-6-9615A>G		intron	N/A	ENSP00000480307.1

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

African (AFR) AF: 0.718 AC: 29797 AN: 41528

American (AMR) AF: 0.467 AC: 7148 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1374 AN: 3472

East Asian (EAS) AF: 0.228 AC: 1177 AN: 5168

South Asian (SAS) AF: 0.402 AC: 1940 AN: 4826

European-Finnish (FIN) AF: 0.481 AC: 5086 AN: 10580

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28002 AN: 67984

Other (OTH) AF: 0.466 AC: 984 AN: 2112

Alfa AF: 0.439 Hom.: 33591

Bravo AF: 0.505

Asia WGS AF: 0.335 AC: 1161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.5
DANN	Benign	0.47
PhyloP100		-0.41

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: rs12907198; hg19: chr15-22916162;