chr12-14628744-G-GAA

Position:

• chr12-14628744-G-GAA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004963.4(GUCY2C):​c.2158-9_2158-8dupTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0074 (12 hom., cov: 0)
  • Exomes 𝑓: 0.0096 (7 hom.)
• Consequence: GUCY2C NM_004963.4 splice_region, 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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-14628744-G-GAA is Benign according to our data. Variant chr12-14628744-G-GAA is described in ClinVar as [Benign]. Clinvar id is 1169657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00744 (1122/150852) while in subpopulation AFR AF= 0.0243 (1000/41136). AF 95% confidence interval is 0.0231. There are 12 homozygotes in gnomad4. There are 545 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GUCY2C	NM_004963.4	c.2158-9_2158-8dupTT		splice_region_variant, intron_variant		ENST00000261170.5	NP_004954.2
GUCY2C	XM_011520631.3	c.1912-9_1912-8dupTT		splice_region_variant, intron_variant			XP_011518933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GUCY2C	ENST00000261170.5	c.2158-9_2158-8dupTT		splice_region_variant, intron_variant		1	NM_004963.4	ENSP00000261170.3

Frequencies

GnomAD3 genomes AF: 0.00730 AC: 1101 AN: 150738 Hom.: 11 Cov.: 0

Gnomad AFR AF: 0.0239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00344

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000389

Gnomad SAS AF: 0.00167

Gnomad FIN AF: 0.0000975

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000783

Gnomad OTH AF: 0.00242

GnomAD4 exome AF: 0.00962 AC: 11092 AN: 1153192 Hom.: 7 Cov.: 20 AF XY: 0.00917 AC XY: 5356 AN XY: 584336

Gnomad4 AFR exome AF: 0.0412

Gnomad4 AMR exome AF: 0.0176

Gnomad4 ASJ exome AF: 0.00716

Gnomad4 EAS exome AF: 0.00277

Gnomad4 SAS exome AF: 0.00792

Gnomad4 FIN exome AF: 0.00379

Gnomad4 NFE exome AF: 0.00918

Gnomad4 OTH exome AF: 0.00961

GnomAD4 genome AF: 0.00744 AC: 1122 AN: 150852 Hom.: 12 Cov.: 0 AF XY: 0.00741 AC XY: 545 AN XY: 73596

Gnomad4 AFR AF: 0.0243

Gnomad4 AMR AF: 0.00344

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000390

Gnomad4 SAS AF: 0.00167

Gnomad4 FIN AF: 0.0000975

Gnomad4 NFE AF: 0.000783

Gnomad4 OTH AF: 0.00239

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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;