rs871012

chr5-157388755-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037333.3(CYFIP2):c.3208-434G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,950 control chromosomes in the GnomAD database, including 15,853 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 0.45 (15853 hom., cov: 32)
• Consequence: CYFIP2 NM_001037333.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460

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]

NIPAL4-DT (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP2	NM_001037333.3	c.3208-434G>C		intron_variant		ENST00000620254.5
NIPAL4-DT	NR_136205.1	n.94-24150C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP2	ENST00000620254.5	c.3208-434G>C		intron_variant		1	NM_001037333.3	P1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68039 AN: 151832 Hom.: 15837 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.391

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.431

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

GnomAD4 genome AF: 0.448 AC: 68095 AN: 151950 Hom.: 15853 Cov.: 32 AF XY: 0.455 AC XY: 33791 AN XY: 74246

Gnomad4 AFR AF: 0.397

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.797

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.391

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.435

Alfa AF: 0.431 Hom.: 1798

Bravo AF: 0.453

Asia WGS AF: 0.691 AC: 2402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.38
Dann	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs871012; hg19: chr5-156815763;