NM_014608.6:c.3597+29A>G

Variant names:

• chr15-22872796-T-C
• rs999842
• NM_014608.6:c.3597+29A>G

Variant summary

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

The NM_014608.6(CYFIP1):​c.3597+29A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 1,608,006 control chromosomes in the GnomAD database, including 249,610 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 0.51 (20599 hom., cov: 32)
  • Exomes 𝑓: 0.56 (229011 hom.)
• Consequence: CYFIP1 NM_014608.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 20 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 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.3597+29A>G		intron	N/A	NP_055423.1
	CYFIP1	NM_001324119.2		c.3699+29A>G		intron	N/A	NP_001311048.1
	CYFIP1	NM_001287810.4		c.3597+29A>G		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.3597+29A>G		intron	N/A	ENSP00000481038.1
	CYFIP1	ENST00000610365.4	TSL:1	c.3597+29A>G		intron	N/A	ENSP00000478779.1
	CYFIP1	ENST00000617556.4	TSL:1	c.2304+29A>G		intron	N/A	ENSP00000480525.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78099 AN: 151868 Hom.: 20598 Cov.: 32

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.414

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.490

GnomAD2 exomes AF: 0.552 AC: 138260 AN: 250408 AF XY: 0.555

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.648

Gnomad FIN exome AF: 0.662

Gnomad NFE exome AF: 0.567

Gnomad OTH exome AF: 0.544

GnomAD4 exome AF: 0.558 AC: 812410 AN: 1456020 Hom.: 229011 Cov.: 31 AF XY: 0.558 AC XY: 404613 AN XY: 724568

African (AFR) AF: 0.383 AC: 12797 AN: 33388

American (AMR) AF: 0.486 AC: 21693 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 10610 AN: 26080

East Asian (EAS) AF: 0.594 AC: 23563 AN: 39648

South Asian (SAS) AF: 0.564 AC: 48515 AN: 86006

European-Finnish (FIN) AF: 0.653 AC: 34856 AN: 53346

Middle Eastern (MID) AF: 0.429 AC: 2467 AN: 5752

European-Non Finnish (NFE) AF: 0.565 AC: 625325 AN: 1106946

Other (OTH) AF: 0.541 AC: 32584 AN: 60202

GnomAD4 genome AF: 0.514 AC: 78129 AN: 151986 Hom.: 20599 Cov.: 32 AF XY: 0.519 AC XY: 38537 AN XY: 74298

African (AFR) AF: 0.392 AC: 16266 AN: 41446

American (AMR) AF: 0.488 AC: 7447 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.414 AC: 1435 AN: 3468

East Asian (EAS) AF: 0.630 AC: 3253 AN: 5166

South Asian (SAS) AF: 0.584 AC: 2808 AN: 4810

European-Finnish (FIN) AF: 0.662 AC: 6983 AN: 10552

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38282 AN: 67970

Other (OTH) AF: 0.488 AC: 1030 AN: 2110

Alfa AF: 0.543 Hom.: 21557

Bravo AF: 0.499

Asia WGS AF: 0.536 AC: 1859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.17
DANN	Benign	0.44
PhyloP100		-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs999842; hg19: chr15-23000272;