12-14669442-T-C

Position:

• chr12-14669442-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004963.4(GUCY2C):​c.1282+280A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.974 in 152,042 control chromosomes in the GnomAD database, including 72,185 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.97 (72185 hom., cov: 28)
• Consequence: GUCY2C NM_004963.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0990

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)

C12orf60 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 12-14669442-T-C is Benign according to our data. Variant chr12-14669442-T-C is described in ClinVar as [Benign]. Clinvar id is 1181182.Status of the report is criteria_provided_single_submitter, 1 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/exons	MANE	Protein	UniProt
GUCY2C	NM_004963.4	c.1282+280A>G		intron_variant		ENST00000261170.5	NP_004954.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCY2C	ENST00000261170.5	c.1282+280A>G		intron_variant		1	NM_004963.4	ENSP00000261170	P1
GUCY2C-AS1	ENST00000501178.2	n.199-2824T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.974 AC: 147926 AN: 151924 Hom.: 72137 Cov.: 28

Gnomad AFR AF: 0.913

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.990

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.985

Gnomad SAS AF: 0.998

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.979

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.974 AC: 148030 AN: 152042 Hom.: 72185 Cov.: 28 AF XY: 0.974 AC XY: 72364 AN XY: 74320

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.990

Gnomad4 ASJ AF: 0.996

Gnomad4 EAS AF: 0.985

Gnomad4 SAS AF: 0.998

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.980

Alfa AF: 0.985 Hom.: 8614

Bravo AF: 0.970

Asia WGS AF: 0.986 AC: 3429 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.67

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

Other links and lift over

dbSNP: rs7398315; hg19: chr12-14822376;