chr5-157382086-G-A

Position:

• chr5-157382086-G-A

Variant summary

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

The NM_001037333.3(CYFIP2):​c.3040-504G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,106 control chromosomes in the GnomAD database, including 903 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 0.10 (903 hom., cov: 32)
• Consequence: CYFIP2 NM_001037333.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP2	NM_001037333.3	c.3040-504G>A		intron_variant		ENST00000620254.5
NIPAL4-DT	NR_136205.1	n.94-17481C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP2	ENST00000620254.5	c.3040-504G>A		intron_variant		1	NM_001037333.3	P1
	ENST00000508443.1	n.727+2127C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15364 AN: 151988 Hom.: 897 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0683

Gnomad ASJ AF: 0.179

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0602

Gnomad FIN AF: 0.0477

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0905

Gnomad OTH AF: 0.0923

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

GnomAD4 genome AF: 0.101 AC: 15388 AN: 152106 Hom.: 903 Cov.: 32 AF XY: 0.0976 AC XY: 7255 AN XY: 74348

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.0682

Gnomad4 ASJ AF: 0.179

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0609

Gnomad4 FIN AF: 0.0477

Gnomad4 NFE AF: 0.0905

Gnomad4 OTH AF: 0.0914

Alfa AF: 0.0976 Hom.: 952

Bravo AF: 0.107

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.40

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: rs884623; hg19: chr5-156809094; COSMIC: COSV59032679; COSMIC: COSV59032679;