chr5-157390258-G-T

Variant names:

• chr5-157390258-G-T
• rs17599222
• NM_001037333.3:c.3447-263G>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.3447-263G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,338 control chromosomes in the GnomAD database, including 20,393 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 (20393 hom., cov: 32)
• Consequence: CYFIP2 NM_001037333.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.594
• Publications: 11 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP2	NM_001037333.3	MANE Select	c.3447-263G>T		intron	N/A	NP_001032410.1
	CYFIP2	NM_001291722.2		c.3522-263G>T		intron	N/A	NP_001278651.1
	CYFIP2	NM_014376.4		c.3447-263G>T		intron	N/A	NP_055191.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYFIP2	ENST00000620254.5	TSL:1 MANE Select	c.3447-263G>T		intron	N/A	ENSP00000479968.1
	CYFIP2	ENST00000616178.4	TSL:1	c.3522-263G>T		intron	N/A	ENSP00000479719.1
	CYFIP2	ENST00000618329.4	TSL:1	c.3447-263G>T		intron	N/A	ENSP00000484819.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 77805 AN: 151220 Hom.: 20373 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.526

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

GnomAD4 genome AF: 0.515 AC: 77875 AN: 151338 Hom.: 20393 Cov.: 32 AF XY: 0.521 AC XY: 38544 AN XY: 73940

African (AFR) AF: 0.469 AC: 19323 AN: 41228

American (AMR) AF: 0.577 AC: 8779 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1835 AN: 3454

East Asian (EAS) AF: 0.798 AC: 4106 AN: 5148

South Asian (SAS) AF: 0.631 AC: 3036 AN: 4808

European-Finnish (FIN) AF: 0.480 AC: 5005 AN: 10422

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.501 AC: 33960 AN: 67782

Other (OTH) AF: 0.530 AC: 1107 AN: 2090

Alfa AF: 0.502 Hom.: 29973

Bravo AF: 0.518

Asia WGS AF: 0.719 AC: 2502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.22
DANN	Benign	0.40
PhyloP100		-0.59
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17599222; hg19: chr5-156817266;