15-22925044-C-T

Variant names:

• chr15-22925044-C-T
• rs6606810
• NM_014608.6:c.1359+938G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014608.6(CYFIP1):​c.1359+938G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,058 control chromosomes in the GnomAD database, including 44,270 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 0.76 (44270 hom., cov: 32)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP1	NM_014608.6	c.1359+938G>A		intron_variant	Intron 13 of 30	ENST00000617928.5	NP_055423.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP1	ENST00000617928.5	c.1359+938G>A		intron_variant	Intron 13 of 30	1	NM_014608.6	ENSP00000481038.1
CYFIP1	ENST00000610365.4	c.1359+938G>A		intron_variant	Intron 14 of 31	1		ENSP00000478779.1
CYFIP1	ENST00000612288.2	c.1359+938G>A		intron_variant	Intron 12 of 29	3		ENSP00000479802.2

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115498 AN: 151940 Hom.: 44216 Cov.: 32

Gnomad AFR AF: 0.837

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.717

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.760 AC: 115614 AN: 152058 Hom.: 44270 Cov.: 32 AF XY: 0.761 AC XY: 56584 AN XY: 74306

African (AFR) AF: 0.837 AC: 34700 AN: 41478

American (AMR) AF: 0.787 AC: 12023 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2746 AN: 3472

East Asian (EAS) AF: 0.681 AC: 3517 AN: 5162

South Asian (SAS) AF: 0.670 AC: 3232 AN: 4824

European-Finnish (FIN) AF: 0.781 AC: 8254 AN: 10566

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.717 AC: 48697 AN: 67958

Other (OTH) AF: 0.727 AC: 1535 AN: 2110

Alfa AF: 0.740 Hom.: 31488

Bravo AF: 0.765

Asia WGS AF: 0.695 AC: 2417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.59
PhyloP100		-0.92

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: rs6606810; hg19: chr15-22948024;