rs7161747

Positions:

• chr15-22927007-A-G

Variant summary

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

The NM_014608.6(CYFIP1):​c.1233+899T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,170 control chromosomes in the GnomAD database, including 2,249 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 0.16 (2249 hom., cov: 33)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP1	NM_014608.6	c.1233+899T>C		intron_variant		ENST00000617928.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP1	ENST00000617928.5	c.1233+899T>C		intron_variant		1	NM_014608.6	P1
CYFIP1	ENST00000610365.4	c.1233+899T>C		intron_variant		1		P1
CYFIP1	ENST00000612288.2	c.1233+899T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23990 AN: 152052 Hom.: 2242 Cov.: 33

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.158 AC: 24019 AN: 152170 Hom.: 2249 Cov.: 33 AF XY: 0.155 AC XY: 11521 AN XY: 74394

Gnomad4 AFR AF: 0.0945

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.107

Gnomad4 SAS AF: 0.113

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.185

Alfa AF: 0.189 Hom.: 3662

Bravo AF: 0.169

Asia WGS AF: 0.0940 AC: 326 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.9
DANN	Benign	0.86

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: rs7161747; hg19: chr15-22946061;