chr5-157269485-C-G

Position:

• chr5-157269485-C-G

Variant summary

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

The ENST00000618329.4(CYFIP2):​c.-122C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,910 control chromosomes in the GnomAD database, including 16,379 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 0.46 (16378 hom., cov: 31)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: CYFIP2 ENST00000618329.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.670

Genes affected

CYFIP2 (HGNC:13760): (cytoplasmic FMR1 interacting protein 2) Predicted to enable small GTPase binding activity. Involved in activation of cysteine-type endopeptidase activity; apoptotic process; and cell-cell adhesion. Located in perinuclear region of cytoplasm and synapse. Part of SCAR complex. Implicated in developmental and epileptic encephalopathy 65. [provided by Alliance of Genome Resources, Apr 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 (EAS) allele frequency at 95% confidence interval = 0.532 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYFIP2	NM_001037333.3	c.-24+3290C>G		intron_variant		ENST00000620254.5	NP_001032410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYFIP2	ENST00000620254.5	c.-24+3290C>G		intron_variant		1	NM_001037333.3	ENSP00000479968	P1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69979 AN: 151776 Hom.: 16377 Cov.: 31

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.474

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.447

GnomAD4 exome AF: 0.500 AC: 8 AN: 16 Hom.: 1 Cov.: 0 AF XY: 0.400 AC XY: 4 AN XY: 10

Gnomad4 ASJ exome AF: 0.00

Gnomad4 NFE exome AF: 0.571

GnomAD4 genome AF: 0.461 AC: 70024 AN: 151894 Hom.: 16378 Cov.: 31 AF XY: 0.461 AC XY: 34241 AN XY: 74224

Gnomad4 AFR AF: 0.379

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.549

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.474

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.444

Alfa AF: 0.332 Hom.: 863

Bravo AF: 0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.5
DANN	Benign	0.65

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: rs767007; hg19: chr5-156696495;