12-14681487-GAA-GA

Variant names:

• chr12-14681487-GA-G
• rs56944147
• NM_004963.4:c.612-11delT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004963.4(GUCY2C):​c.612-11delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (67306 hom., cov: 0)
  • Exomes 𝑓: 0.99 (717027 hom.)
• Consequence: GUCY2C NM_004963.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.225
• Publications: 7 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 12-14681487-GA-G is Benign according to our data. Variant chr12-14681487-GA-G is described in ClinVar as [Benign]. Clinvar id is 402917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GUCY2C	NM_004963.4	c.612-11delT		intron_variant	Intron 4 of 26	ENST00000261170.5	NP_004954.2
GUCY2C-AS1	NR_186173.1	n.384+9178delA		intron_variant	Intron 4 of 5
GUCY2C	XM_011520631.3	c.366-11delT		intron_variant	Intron 4 of 26		XP_011518933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GUCY2C	ENST00000261170.5	c.612-11delT		intron_variant	Intron 4 of 26	1	NM_004963.4	ENSP00000261170.3

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142111 AN: 151814 Hom.: 67271 Cov.: 0

Gnomad AFR AF: 0.782

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.975

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.997

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.954

GnomAD2 exomes AF: 0.981 AC: 245163 AN: 249906 AF XY: 0.986

Gnomad AFR exome AF: 0.773

Gnomad AMR exome AF: 0.989

Gnomad ASJ exome AF: 0.990

Gnomad EAS exome AF: 0.985

Gnomad FIN exome AF: 0.996

Gnomad NFE exome AF: 0.998

Gnomad OTH exome AF: 0.990

GnomAD4 exome AF: 0.992 AC: 1443284 AN: 1454380 Hom.: 717027 Cov.: 0 AF XY: 0.993 AC XY: 719115 AN XY: 724016

African (AFR) AF: 0.772 AC: 25571 AN: 33122

American (AMR) AF: 0.987 AC: 43811 AN: 44372

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 25746 AN: 25992

East Asian (EAS) AF: 0.983 AC: 38971 AN: 39632

South Asian (SAS) AF: 0.999 AC: 85834 AN: 85924

European-Finnish (FIN) AF: 0.997 AC: 53191 AN: 53360

Middle Eastern (MID) AF: 0.986 AC: 5661 AN: 5742

European-Non Finnish (NFE) AF: 0.999 AC: 1105377 AN: 1106094

Other (OTH) AF: 0.983 AC: 59122 AN: 60142

GnomAD4 genome AF: 0.936 AC: 142202 AN: 151932 Hom.: 67306 Cov.: 0 AF XY: 0.937 AC XY: 69602 AN XY: 74260

African (AFR) AF: 0.782 AC: 32322 AN: 41324

American (AMR) AF: 0.975 AC: 14870 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.989 AC: 3433 AN: 3470

East Asian (EAS) AF: 0.985 AC: 5100 AN: 5176

South Asian (SAS) AF: 0.998 AC: 4800 AN: 4812

European-Finnish (FIN) AF: 0.996 AC: 10566 AN: 10604

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67900 AN: 67978

Other (OTH) AF: 0.954 AC: 2011 AN: 2108

Alfa AF: 0.971 Hom.: 13063

Bravo AF: 0.928

Asia WGS AF: 0.977 AC: 3399 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital diarrhea 6 Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs56944147; hg19: chr12-14834421; COSMIC: COSV108796061;