rs7161747

Variant names:

• chr15-22927007-A-G
• rs7161747
• NM_014608.6:c.1233+899T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.79).
• 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 rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.1233+899T>C		intron_variant	Intron 12 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.1233+899T>C		intron_variant	Intron 12 of 30	1	NM_014608.6	ENSP00000481038.1
CYFIP1	ENST00000610365.4	c.1233+899T>C		intron_variant	Intron 13 of 31	1		ENSP00000478779.1
CYFIP1	ENST00000612288.2	c.1233+899T>C		intron_variant	Intron 11 of 29	3		ENSP00000479802.2

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

African (AFR) AF: 0.0945 AC: 3923 AN: 41516

American (AMR) AF: 0.256 AC: 3902 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 629 AN: 3470

East Asian (EAS) AF: 0.107 AC: 553 AN: 5176

South Asian (SAS) AF: 0.113 AC: 544 AN: 4824

European-Finnish (FIN) AF: 0.111 AC: 1174 AN: 10606

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.188 AC: 12754 AN: 67996

Other (OTH) AF: 0.185 AC: 390 AN: 2110

Alfa AF: 0.187 Hom.: 4670

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
PhyloP100		0.24

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: rs7161747; hg19: chr15-22946061;