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GeneBe

5-157285442-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_001037333.3(CYFIP2):c.81A>G(p.Pro27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,579,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000081 ( 0 hom. )

Consequence

CYFIP2
NM_001037333.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.37
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 5-157285442-A-G is Benign according to our data. Variant chr5-157285442-A-G is described in ClinVar as [Benign]. Clinvar id is 1599679.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=2.37 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000611 (93/152246) while in subpopulation AFR AF= 0.00209 (87/41552). AF 95% confidence interval is 0.00174. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 94 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CYFIP2NM_001037333.3 linkuse as main transcriptc.81A>G p.Pro27= synonymous_variant 2/31 ENST00000620254.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CYFIP2ENST00000620254.5 linkuse as main transcriptc.81A>G p.Pro27= synonymous_variant 2/311 NM_001037333.3 P1Q96F07-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000618
AC:
94
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00210
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000960
GnomAD3 exomes
AF:
0.000214
AC:
42
AN:
196548
Hom.:
0
AF XY:
0.000191
AC XY:
20
AN XY:
104638
show subpopulations
Gnomad AFR exome
AF:
0.00249
Gnomad AMR exome
AF:
0.000387
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000234
Gnomad OTH exome
AF:
0.000194
GnomAD4 exome
AF:
0.0000806
AC:
115
AN:
1426866
Hom.:
0
Cov.:
31
AF XY:
0.0000793
AC XY:
56
AN XY:
706110
show subpopulations
Gnomad4 AFR exome
AF:
0.00245
Gnomad4 AMR exome
AF:
0.000305
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000247
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000548
Gnomad4 OTH exome
AF:
0.000186
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000611
AC:
93
AN:
152246
Hom.:
0
Cov.:
32
AF XY:
0.000551
AC XY:
41
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.00209
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000950
Alfa
AF:
0.000346
Hom.:
0
Bravo
AF:
0.000725
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 24, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.32
Cadd
Benign
12
Dann
Benign
0.82
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs367998009; hg19: chr5-156712452; API