chr15-22963861-G-A

Variant names:

• chr15-22963861-G-A
• rs7175101
• NM_014608.6:c.-7+16426C>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.-7+16426C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 151,930 control chromosomes in the GnomAD database, including 21,392 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 0.52 (21392 hom., cov: 31)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.621 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.-7+16426C>T		intron	N/A	NP_055423.1
	CYFIP1	NM_001324119.2		c.97-16570C>T		intron	N/A	NP_001311048.1
	CYFIP1	NM_001287810.4		c.-125-15832C>T		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.-7+16426C>T		intron	N/A	ENSP00000481038.1
	CYFIP1	ENST00000610365.4	TSL:1	c.-125-15832C>T		intron	N/A	ENSP00000478779.1
	CYFIP1	ENST00000613006.4	TSL:4	c.-6-16570C>T		intron	N/A	ENSP00000480307.1

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79458 AN: 151812 Hom.: 21352 Cov.: 31

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.424

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.507

Gnomad OTH AF: 0.514

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

GnomAD4 genome AF: 0.524 AC: 79549 AN: 151930 Hom.: 21392 Cov.: 31 AF XY: 0.521 AC XY: 38665 AN XY: 74258

African (AFR) AF: 0.627 AC: 25986 AN: 41412

American (AMR) AF: 0.392 AC: 5989 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1783 AN: 3472

East Asian (EAS) AF: 0.391 AC: 2013 AN: 5142

South Asian (SAS) AF: 0.424 AC: 2047 AN: 4826

European-Finnish (FIN) AF: 0.542 AC: 5720 AN: 10556

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.507 AC: 34433 AN: 67946

Other (OTH) AF: 0.514 AC: 1083 AN: 2108

Alfa AF: 0.505 Hom.: 31287

Bravo AF: 0.518

Asia WGS AF: 0.387 AC: 1349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.35
DANN	Benign	0.37
PhyloP100		-0.38

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: rs7175101; hg19: chr15-22909207;