15-22939377-C-T

Variant names:

• chr15-22939377-C-T
• rs1109036
• NM_014608.6:c.666+34G>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.666+34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,613,528 control chromosomes in the GnomAD database, including 63,651 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 0.24 (4764 hom., cov: 30)
  • Exomes 𝑓: 0.28 (58887 hom.)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.316 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.666+34G>A		intron	N/A	NP_055423.1
	CYFIP1	NM_001324119.2		c.768+34G>A		intron	N/A	NP_001311048.1
	CYFIP1	NM_001287810.4		c.666+34G>A		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.666+34G>A		intron	N/A	ENSP00000481038.1
	CYFIP1	ENST00000610365.4	TSL:1	c.666+34G>A		intron	N/A	ENSP00000478779.1
	CYFIP1	ENST00000612288.2	TSL:3	c.666+34G>A		intron	N/A	ENSP00000479802.2

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35718 AN: 151722 Hom.: 4755 Cov.: 30

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.274

GnomAD2 exomes AF: 0.279 AC: 70167 AN: 251400 AF XY: 0.271

Gnomad AFR exome AF: 0.106

Gnomad AMR exome AF: 0.421

Gnomad ASJ exome AF: 0.218

Gnomad EAS exome AF: 0.303

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.295

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.279 AC: 407647 AN: 1461688 Hom.: 58887 Cov.: 38 AF XY: 0.276 AC XY: 200592 AN XY: 727118

African (AFR) AF: 0.108 AC: 3631 AN: 33478

American (AMR) AF: 0.408 AC: 18254 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 5776 AN: 26134

East Asian (EAS) AF: 0.265 AC: 10530 AN: 39698

South Asian (SAS) AF: 0.161 AC: 13875 AN: 86256

European-Finnish (FIN) AF: 0.270 AC: 14430 AN: 53408

Middle Eastern (MID) AF: 0.298 AC: 1720 AN: 5768

European-Non Finnish (NFE) AF: 0.291 AC: 323511 AN: 1111842

Other (OTH) AF: 0.264 AC: 15920 AN: 60386

GnomAD4 genome AF: 0.235 AC: 35741 AN: 151840 Hom.: 4764 Cov.: 30 AF XY: 0.235 AC XY: 17412 AN XY: 74194

African (AFR) AF: 0.111 AC: 4603 AN: 41436

American (AMR) AF: 0.323 AC: 4928 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 787 AN: 3472

East Asian (EAS) AF: 0.294 AC: 1508 AN: 5136

South Asian (SAS) AF: 0.148 AC: 714 AN: 4822

European-Finnish (FIN) AF: 0.266 AC: 2801 AN: 10534

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.286 AC: 19417 AN: 67892

Other (OTH) AF: 0.275 AC: 579 AN: 2104

Alfa AF: 0.255 Hom.: 1181

Bravo AF: 0.242

Asia WGS AF: 0.205 AC: 711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.1
DANN	Benign	0.79
PhyloP100		0.078

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: rs1109036; hg19: chr15-22933691;