NM_001037333.3:c.3040-504G>A

Variant names:

• chr5-157382086-G-A
• rs884623
• NM_001037333.3:c.3040-504G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 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.3040-504G>A		intron	N/A	NP_001032410.1	Q96F07-2
	CYFIP2	NM_001291722.2		c.3115-504G>A		intron	N/A	NP_001278651.1	Q96F07-1
	CYFIP2	NM_014376.4		c.3040-504G>A		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.3040-504G>A		intron	N/A	ENSP00000479968.1	Q96F07-2
	CYFIP2	ENST00000616178.4	TSL:1	c.3115-504G>A		intron	N/A	ENSP00000479719.1	Q96F07-1
	CYFIP2	ENST00000618329.4	TSL:1	c.3040-504G>A		intron	N/A	ENSP00000484819.1	Q96F07-2

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

African (AFR) AF: 0.155 AC: 6408 AN: 41466

American (AMR) AF: 0.0682 AC: 1042 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 621 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0609 AC: 294 AN: 4826

European-Finnish (FIN) AF: 0.0477 AC: 504 AN: 10574

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0905 AC: 6155 AN: 67990

Other (OTH) AF: 0.0914 AC: 193 AN: 2112

Alfa AF: 0.0986 Hom.: 1185

Bravo AF: 0.107

Asia WGS AF: 0.0400 AC: 140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.40
PhyloP100		-0.20
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: rs884623; hg19: chr5-156809094; COSMIC: COSV59032679; COSMIC: COSV59032679;