5-157390368-C-T

Variant names:

• chr5-157390368-C-T
• rs7724666
• NM_001037333.3:c.3447-153C>T

Variant summary

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

The NM_001037333.3(CYFIP2):​c.3447-153C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,088 control chromosomes in the GnomAD database, including 1,206 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 0.12 (1206 hom., cov: 32)
• Consequence: CYFIP2 NM_001037333.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 3 publications found

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]

ENSG00000285868 (HGNC:):

NIPAL4-DT (HGNC:55542): (NIPAL4 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037333.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP2	NM_001037333.3	MANE Select	c.3447-153C>T		intron	N/A	NP_001032410.1	Q96F07-2
	CYFIP2	NM_001291722.2		c.3522-153C>T		intron	N/A	NP_001278651.1	Q96F07-1
	CYFIP2	NM_014376.4		c.3447-153C>T		intron	N/A	NP_055191.2	Q96F07-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP2	ENST00000620254.5	TSL:1 MANE Select	c.3447-153C>T		intron	N/A	ENSP00000479968.1	Q96F07-2
	CYFIP2	ENST00000616178.4	TSL:1	c.3522-153C>T		intron	N/A	ENSP00000479719.1	Q96F07-1
	CYFIP2	ENST00000618329.4	TSL:1	c.3447-153C>T		intron	N/A	ENSP00000484819.1	Q96F07-2

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17701 AN: 151970 Hom.: 1204 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0710

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.00772

Gnomad SAS AF: 0.0522

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.117 AC: 17722 AN: 152088 Hom.: 1206 Cov.: 32 AF XY: 0.113 AC XY: 8431 AN XY: 74340

African (AFR) AF: 0.164 AC: 6785 AN: 41460

American (AMR) AF: 0.0709 AC: 1084 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 479 AN: 3470

East Asian (EAS) AF: 0.00774 AC: 40 AN: 5170

South Asian (SAS) AF: 0.0529 AC: 255 AN: 4822

European-Finnish (FIN) AF: 0.127 AC: 1342 AN: 10560

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7419 AN: 68000

Other (OTH) AF: 0.114 AC: 241 AN: 2108

Alfa AF: 0.102 Hom.: 1090

Bravo AF: 0.114

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs7724666; hg19: chr5-156817376;