5-157381348-C-T

Variant names:

• chr5-157381348-C-T
• rs6555977
• NM_001037333.3:c.3040-1242C>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.3040-1242C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 150,838 control chromosomes in the GnomAD database, including 61,940 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 0.90 (61940 hom., cov: 25)
• Consequence: CYFIP2 NM_001037333.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 2 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYFIP2	NM_001037333.3	c.3040-1242C>T		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.3040-1242C>T		intron_variant	Intron 26 of 30	1	NM_001037333.3	ENSP00000479968.1
ENSG00000285868	ENST00000519499.2	c.-2232-4842G>A		intron_variant	Intron 1 of 5	3		ENSP00000496943.1

Frequencies

GnomAD3 genomes AF: 0.904 AC: 136315 AN: 150724 Hom.: 61879 Cov.: 25

Gnomad AFR AF: 0.974

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.955

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.973

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.972

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.922

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

GnomAD4 genome AF: 0.905 AC: 136434 AN: 150838 Hom.: 61940 Cov.: 25 AF XY: 0.906 AC XY: 66680 AN XY: 73628

African (AFR) AF: 0.975 AC: 40000 AN: 41044

American (AMR) AF: 0.868 AC: 13181 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.955 AC: 3312 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5156 AN: 5156

South Asian (SAS) AF: 0.974 AC: 4631 AN: 4756

European-Finnish (FIN) AF: 0.847 AC: 8574 AN: 10118

Middle Eastern (MID) AF: 0.973 AC: 286 AN: 294

European-Non Finnish (NFE) AF: 0.863 AC: 58543 AN: 67826

Other (OTH) AF: 0.923 AC: 1921 AN: 2082

Alfa AF: 0.882 Hom.: 49787

Bravo AF: 0.907

Asia WGS AF: 0.980 AC: 3408 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.64
DANN	Benign	0.21
PhyloP100		-1.3
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: rs6555977; hg19: chr5-156808356; COSMIC: COSV59032657; COSMIC: COSV59032657;