rs728693

chr5-157365280-G-A

Variant summary

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

The NM_001037333.3(CYFIP2):c.3039+3682G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,016 control chromosomes in the GnomAD database, including 22,425 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 0.53 (22425 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: CYFIP2 NM_001037333.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.702

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:55542): (NIPAL4 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.62 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYFIP2	NM_001037333.3	c.3039+3682G>A		intron_variant		ENST00000620254.5
NIPAL4-DT	NR_136205.1	n.94-675C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYFIP2	ENST00000620254.5	c.3039+3682G>A		intron_variant		1	NM_001037333.3	P1
NIPAL4-DT	ENST00000509655.2	n.222C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80878 AN: 151898 Hom.: 22412 Cov.: 32

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.564

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.552

Gnomad OTH AF: 0.533

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.532 AC: 80944 AN: 152016 Hom.: 22425 Cov.: 32 AF XY: 0.518 AC XY: 38481 AN XY: 74304

Gnomad4 AFR AF: 0.627

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.564

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.552

Gnomad4 OTH AF: 0.530

Alfa AF: 0.543 Hom.: 12142

Bravo AF: 0.538

Asia WGS AF: 0.255 AC: 888 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	4.1
Dann	Benign	0.38

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: rs728693; hg19: chr5-156792288;