12-14669726-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The ENST00000261170.5(GUCY2C):​c.1278C>T​(p.Gly426=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000268 in 1,495,268 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 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

GUCY2C
ENST00000261170.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.168
Variant links:
Genes affected
GUCY2C (HGNC:4688): (guanylate cyclase 2C) This gene encodes a transmembrane protein that functions as a receptor for endogenous peptides guanylin and uroguanylin, and the heat-stable E. coli enterotoxin. The encoded protein activates the cystic fibrosis transmembrane conductance regulator. Mutations in this gene are associated with familial diarrhea (autosomal dominant) and meconium ileus (autosomal recessive). [provided by RefSeq, Nov 2016]
GUCY2C-AS1 (HGNC:56054): (GUCY2C antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.73).
BP6
Variant 12-14669726-G-A is Benign according to our data. Variant chr12-14669726-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2971608.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.168 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GUCY2CNM_004963.4 linkuse as main transcriptc.1278C>T p.Gly426= synonymous_variant 10/27 ENST00000261170.5 NP_004954.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GUCY2CENST00000261170.5 linkuse as main transcriptc.1278C>T p.Gly426= synonymous_variant 10/271 NM_004963.4 ENSP00000261170 P1
GUCY2C-AS1ENST00000501178.2 linkuse as main transcriptn.199-2540G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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:
0.00
GnomAD4 exome
AF:
0.00000223
AC:
3
AN:
1343146
Hom.:
0
Cov.:
19
AF XY:
0.00000148
AC XY:
1
AN XY:
674530
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000237
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000355
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74288
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
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:
0.00
Bravo
AF:
0.0000189

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 testingLabcorp Genetics (formerly Invitae), LabcorpDec 17, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.73
CADD
Benign
8.3
DANN
Benign
0.76

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.15
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: rs751905574; hg19: chr12-14822660; API