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GeneBe

3-130686401-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_014602.3(PIK3R4):c.3285C>T(p.Asp1095=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,609,616 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

PIK3R4
NM_014602.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0480
Variant links:
Genes affected
PIK3R4 (HGNC:8982): (phosphoinositide-3-kinase regulatory subunit 4) Predicted to enable protein serine/threonine kinase activity. Involved in positive regulation of phosphatidylinositol 3-kinase activity; receptor catabolic process; and regulation of cytokinesis. Located in late endosome and microtubule cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 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=-0.57).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-130686401-G-A is Benign according to our data. Variant chr3-130686401-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 741903.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=0.048 with no splicing effect.
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 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PIK3R4NM_014602.3 linkuse as main transcriptc.3285C>T p.Asp1095= synonymous_variant 15/20 ENST00000356763.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PIK3R4ENST00000356763.8 linkuse as main transcriptc.3285C>T p.Asp1095= synonymous_variant 15/201 NM_014602.3 P1
PIK3R4ENST00000512362.5 linkuse as main transcriptn.15C>T non_coding_transcript_exon_variant 1/52
PIK3R4ENST00000512677.1 linkuse as main transcriptn.190C>T non_coding_transcript_exon_variant 2/63

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000112
AC:
17
AN:
152112
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000830
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000132
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000188
AC:
47
AN:
250644
Hom.:
0
AF XY:
0.000251
AC XY:
34
AN XY:
135442
show subpopulations
Gnomad AFR exome
AF:
0.0000616
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00124
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000707
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000131
AC:
191
AN:
1457386
Hom.:
0
Cov.:
29
AF XY:
0.000175
AC XY:
127
AN XY:
725308
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00122
Gnomad4 FIN exome
AF:
0.0000374
Gnomad4 NFE exome
AF:
0.0000686
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000118
AC:
18
AN:
152230
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74434
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000830
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000132
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000113
Hom.:
0
Bravo
AF:
0.0000793
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0000546
EpiControl
AF:
0.0000593

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeOct 10, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.57
Cadd
Benign
1.4
Dann
Benign
0.46

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs139162560; hg19: chr3-130405245; API