NM_004963.4:c.1282+280A>G

Variant names:

• chr12-14669442-T-C
• rs7398315
• NM_004963.4:c.1282+280A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004963.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY2C	NM_004963.4	MANE Select	c.1282+280A>G		intron	N/A	NP_004954.2	P25092
	GUCY2C-AS1	NR_186173.1		n.335+1296T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GUCY2C	ENST00000261170.5	TSL:1 MANE Select	c.1282+280A>G		intron	N/A	ENSP00000261170.3	P25092
	GUCY2C	ENST00000867619.1		c.1282+280A>G		intron	N/A	ENSP00000537678.1
	GUCY2C	ENST00000970783.1		c.1282+280A>G		intron	N/A	ENSP00000640842.1

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

African (AFR) AF: 0.912 AC: 37788 AN: 41414

American (AMR) AF: 0.990 AC: 15125 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3457 AN: 3470

East Asian (EAS) AF: 0.985 AC: 5083 AN: 5160

South Asian (SAS) AF: 0.998 AC: 4797 AN: 4808

European-Finnish (FIN) AF: 0.996 AC: 10550 AN: 10588

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.999 AC: 67958 AN: 68002

Other (OTH) AF: 0.980 AC: 2067 AN: 2110

Alfa AF: 0.983 Hom.: 8944

Bravo AF: 0.970

Asia WGS AF: 0.986 AC: 3429 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.9
DANN	Benign	0.67
PhyloP100		-0.099
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7398315; hg19: chr12-14822376;