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GeneBe

7-133253161-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4BP6_ModerateBP7BS1BS2

The NM_021807.4(EXOC4):c.60C>T(p.Pro20=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0019 in 1,614,170 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.010 ( 36 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 27 hom. )

Consequence

EXOC4
NM_021807.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.237
Variant links:
Genes affected
EXOC4 (HGNC:30389): (exocyst complex component 4) The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and functions of exocyst complex have been demonstrated to be highly conserved in higher eukaryotes. At least eight components of the exocyst complex, including this protein, are found to interact with the actin cytoskeletal remodeling and vesicle transport machinery. The complex is also essential for the biogenesis of epithelial cell surface polarity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 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=-0.16).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-133253161-C-T is Benign according to our data. Variant chr7-133253161-C-T is described in ClinVar as [Benign]. Clinvar id is 781114.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=0.237 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 = 0.0103 (1571/152318) while in subpopulation AFR AF= 0.0366 (1523/41574). AF 95% confidence interval is 0.0351. There are 36 homozygotes in gnomad4. There are 729 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 Homozygotes in GnomAd at 36 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
EXOC4NM_021807.4 linkuse as main transcriptc.60C>T p.Pro20= synonymous_variant 1/18 ENST00000253861.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
EXOC4ENST00000253861.5 linkuse as main transcriptc.60C>T p.Pro20= synonymous_variant 1/181 NM_021807.4 P1Q96A65-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0103
AC:
1569
AN:
152200
Hom.:
36
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0367
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00262
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:
0.0000441
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.00266
AC:
668
AN:
251236
Hom.:
14
AF XY:
0.00177
AC XY:
240
AN XY:
135776
show subpopulations
Gnomad AFR exome
AF:
0.0381
Gnomad AMR exome
AF:
0.000983
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000705
Gnomad OTH exome
AF:
0.000652
GnomAD4 exome
AF:
0.00102
AC:
1494
AN:
1461852
Hom.:
27
Cov.:
30
AF XY:
0.000828
AC XY:
602
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.0394
Gnomad4 AMR exome
AF:
0.00107
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.00156
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0103
AC:
1571
AN:
152318
Hom.:
36
Cov.:
32
AF XY:
0.00979
AC XY:
729
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.0366
Gnomad4 AMR
AF:
0.00261
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00274
Hom.:
0
Bravo
AF:
0.0112
Asia WGS
AF:
0.00231
AC:
9
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

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 testingInvitaeMay 03, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.16
Cadd
Benign
12
Dann
Benign
0.88

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: rs73436933; hg19: chr7-132937917; API