12-14613216-C-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS1

The NM_004963.4(GUCY2C):ā€‹c.3123G>Cā€‹(p.Gly1041Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000403 in 1,613,408 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0014 ( 0 hom., cov: 32)
Exomes š‘“: 0.00030 ( 0 hom. )

Consequence

GUCY2C
NM_004963.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41
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]
PLBD1-AS1 (HGNC:51143): (PLBD1 antisense RNA 1)

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 12-14613216-C-G is Benign according to our data. Variant chr12-14613216-C-G is described in ClinVar as [Benign]. Clinvar id is 735631.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.41 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00141 (214/152216) while in subpopulation AFR AF= 0.00438 (182/41558). AF 95% confidence interval is 0.00386. There are 0 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GUCY2CNM_004963.4 linkc.3123G>C p.Gly1041Gly synonymous_variant Exon 27 of 27 ENST00000261170.5 NP_004954.2 P25092
GUCY2CXM_011520631.3 linkc.2877G>C p.Gly959Gly synonymous_variant Exon 27 of 27 XP_011518933.1
PLBD1-AS1NR_120465.1 linkn.297+290C>G intron_variant Intron 3 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GUCY2CENST00000261170.5 linkc.3123G>C p.Gly1041Gly synonymous_variant Exon 27 of 27 1 NM_004963.4 ENSP00000261170.3 P25092
PLBD1-AS1ENST00000542401.2 linkn.848+290C>G intron_variant Intron 2 of 4 4
PLBD1-AS1ENST00000545424.5 linkn.279+290C>G intron_variant Intron 3 of 4 3
PLBD1-AS1ENST00000660979.1 linkn.732-5936C>G intron_variant Intron 1 of 3

Frequencies

GnomAD3 genomes
AF:
0.00141
AC:
214
AN:
152098
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00439
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00634
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00144
GnomAD3 exomes
AF:
0.000649
AC:
163
AN:
251170
Hom.:
0
AF XY:
0.000619
AC XY:
84
AN XY:
135746
show subpopulations
Gnomad AFR exome
AF:
0.00443
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00685
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000141
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000298
AC:
436
AN:
1461192
Hom.:
0
Cov.:
30
AF XY:
0.000285
AC XY:
207
AN XY:
726932
show subpopulations
Gnomad4 AFR exome
AF:
0.00505
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00655
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000477
Gnomad4 OTH exome
AF:
0.000597
GnomAD4 genome
AF:
0.00141
AC:
214
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.00155
AC XY:
115
AN XY:
74414
show subpopulations
Gnomad4 AFR
AF:
0.00438
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00634
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.00116
Hom.:
0
Bravo
AF:
0.00159
EpiCase
AF:
0.000327
EpiControl
AF:
0.000296

ClinVar

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

Submissions by phenotype

not provided Benign:1
Jan 07, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
0.94
DANN
Benign
0.50

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: rs11056059; hg19: chr12-14766150; API