rs777188684

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001407446.1(APC):​c.22G>A​(p.Gly8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,370,666 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000026 ( 1 hom. )

Consequence

APC
NM_001407446.1 missense

Scores

1
2
10

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.854
Variant links:
Genes affected
APC (HGNC:583): (APC regulator of WNT signaling pathway) This gene encodes a tumor suppressor protein that acts as an antagonist of the Wnt signaling pathway. It is also involved in other processes including cell migration and adhesion, transcriptional activation, and apoptosis. Defects in this gene cause familial adenomatous polyposis (FAP), an autosomal dominant pre-malignant disease that usually progresses to malignancy. Mutations in the APC gene have been found to occur in most colorectal cancers, where disease-associated mutations tend to be clustered in a small region designated the mutation cluster region (MCR) and result in a truncated protein product. [provided by RefSeq, Jun 2022]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.124177754).
BP6
Variant 5-112707739-G-A is Benign according to our data. Variant chr5-112707739-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 537575.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 32 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
APCNM_001407446.1 linkc.22G>A p.Gly8Ser missense_variant Exon 1 of 16 NP_001394375.1
APCNM_001354897.2 linkc.22G>A p.Gly8Ser missense_variant Exon 1 of 15 NP_001341826.1
APCNM_001127511.3 linkc.22G>A p.Gly8Ser missense_variant Exon 1 of 14 NP_001120983.2 P25054-3Q4LE70

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
APCENST00000507379.6 linkc.22G>A p.Gly8Ser missense_variant Exon 1 of 14 2 ENSP00000423224.2 A0A2Q2SV78
APCENST00000509732.6 linkc.-19+90G>A intron_variant Intron 1 of 15 4 ENSP00000426541.2 D6RFL6
APCENST00000505350.2 linkn.22G>A non_coding_transcript_exon_variant Exon 1 of 16 3 ENSP00000481752.1 A0A087WYF3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152172
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000955
AC:
13
AN:
136182
Hom.:
1
AF XY:
0.0000946
AC XY:
7
AN XY:
74030
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000578
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000263
AC:
32
AN:
1218376
Hom.:
1
Cov.:
31
AF XY:
0.0000336
AC XY:
20
AN XY:
595228
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:
0.000403
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000207
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152290
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000621
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000426
AC:
1

ClinVar

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

Submissions by phenotype

Familial adenomatous polyposis 1 Benign:1
Nov 07, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.085
T
BayesDel_noAF
Uncertain
0.0
CADD
Benign
17
DANN
Uncertain
0.99
Eigen
Benign
-0.32
Eigen_PC
Benign
-0.33
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.59
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-0.38
T
PROVEAN
Benign
0.060
N
REVEL
Benign
0.27
Sift
Pathogenic
0.0
D
MutPred
0.17
Gain of glycosylation at G8 (P = 0.0043);
MVP
0.88
ClinPred
0.38
T
GERP RS
-1.1

Splicing

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: rs777188684; hg19: chr5-112043436; API