rs3217210

Positions:

• chr12-14628744-GA-G
• chr12-14628744-GA-GAA
• chr12-14628744-GA-GAAA
• chr12-14628744-GA-GAAAA

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004963.4(GUCY2C):​c.2158-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00080 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00088 (4 hom.)
• Consequence: GUCY2C NM_004963.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.995

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]

C12orf60 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 12-14628744-GA-G is Benign according to our data. Variant chr12-14628744-GA-G is described in ClinVar as [Benign]. Clinvar id is 1668452.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-14628744-GA-G is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome4 at 4 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GUCY2C	NM_004963.4	c.2158-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261170.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GUCY2C	ENST00000261170.5	c.2158-8del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004963.4	P1

Frequencies

GnomAD3 genomes AF: 0.000803 AC: 121 AN: 150766 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000585

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.000331

Gnomad ASJ AF: 0.00781

Gnomad EAS AF: 0.000972

Gnomad SAS AF: 0.000836

Gnomad FIN AF: 0.0000975

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000783

Gnomad OTH AF: 0.000484

GnomAD3 exomes AF: 0.000867 AC: 188 AN: 216742 Hom.: 1 AF XY: 0.000874 AC XY: 103 AN XY: 117828

Gnomad AFR exome AF: 0.000721

Gnomad AMR exome AF: 0.000112

Gnomad ASJ exome AF: 0.00731

Gnomad EAS exome AF: 0.00128

Gnomad SAS exome AF: 0.000467

Gnomad FIN exome AF: 0.000154

Gnomad NFE exome AF: 0.000684

Gnomad OTH exome AF: 0.00135

GnomAD4 exome AF: 0.000880 AC: 1046 AN: 1188842 Hom.: 4 Cov.: 20 AF XY: 0.000899 AC XY: 542 AN XY: 603030

Gnomad4 AFR exome AF: 0.000646

Gnomad4 AMR exome AF: 0.000173

Gnomad4 ASJ exome AF: 0.00672

Gnomad4 EAS exome AF: 0.00100

Gnomad4 SAS exome AF: 0.000463

Gnomad4 FIN exome AF: 0.000214

Gnomad4 NFE exome AF: 0.000825

Gnomad4 OTH exome AF: 0.00110

GnomAD4 genome AF: 0.000802 AC: 121 AN: 150880 Hom.: 0 Cov.: 0 AF XY: 0.000720 AC XY: 53 AN XY: 73614

Gnomad4 AFR AF: 0.000583

Gnomad4 AMR AF: 0.000330

Gnomad4 ASJ AF: 0.00781

Gnomad4 EAS AF: 0.000974

Gnomad4 SAS AF: 0.000837

Gnomad4 FIN AF: 0.0000975

Gnomad4 NFE AF: 0.000783

Gnomad4 OTH AF: 0.000478

Alfa AF: 0.000552 Hom.: 8258

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

Invitae

Dec 28, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: rs3217210; hg19: chr12-14781678;