chr5-157381348-C-T

Position:

• chr5-157381348-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CYFIP2	NM_001037333.3	c.3040-1242C>T		intron_variant		ENST00000620254.5	NP_001032410.1
NIPAL4-DT	NR_136205.1	n.94-16743G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYFIP2	ENST00000620254.5	c.3040-1242C>T		intron_variant		1	NM_001037333.3	ENSP00000479968	P1
	ENST00000508443.1	n.727+2865G>A		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.975

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.955

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.974

Gnomad4 FIN AF: 0.847

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.923

Alfa AF: 0.881 Hom.: 37373

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

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: rs6555977; hg19: chr5-156808356; COSMIC: COSV59032657; COSMIC: COSV59032657;