5-157378278-A-G

Variant names:

• chr5-157378278-A-G
• rs10515748
• NM_001037333.3:c.3040-4312A>G

Variant summary

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

The NM_001037333.3(CYFIP2):​c.3040-4312A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 152,260 control chromosomes in the GnomAD database, including 1,148 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 0.11 (1148 hom., cov: 32)
• Consequence: CYFIP2 NM_001037333.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP2	NM_001037333.3	c.3040-4312A>G		intron_variant	Intron 26 of 30	ENST00000620254.5	NP_001032410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYFIP2	ENST00000620254.5	c.3040-4312A>G		intron_variant	Intron 26 of 30	1	NM_001037333.3	ENSP00000479968.1
ENSG00000285868	ENST00000519499.2	c.-2232-1772T>C		intron_variant	Intron 1 of 5	3		ENSP00000496943.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16752 AN: 152142 Hom.: 1149 Cov.: 32

Gnomad AFR AF: 0.0250

Gnomad AMI AF: 0.169

Gnomad AMR AF: 0.0800

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.174

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.0975

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

GnomAD4 genome AF: 0.110 AC: 16747 AN: 152260 Hom.: 1148 Cov.: 32 AF XY: 0.114 AC XY: 8516 AN XY: 74428

African (AFR) AF: 0.0249 AC: 1037 AN: 41576

American (AMR) AF: 0.0800 AC: 1224 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 736 AN: 3470

East Asian (EAS) AF: 0.174 AC: 901 AN: 5174

South Asian (SAS) AF: 0.187 AC: 900 AN: 4818

European-Finnish (FIN) AF: 0.202 AC: 2136 AN: 10588

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9422 AN: 68008

Other (OTH) AF: 0.0970 AC: 205 AN: 2114

Alfa AF: 0.0833 Hom.: 271

Bravo AF: 0.0980

Asia WGS AF: 0.136 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.2
DANN	Benign	0.86
PhyloP100		-0.23
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: rs10515748; hg19: chr5-156805286; COSMIC: COSV59032602; COSMIC: COSV59032602;