rs1320052

Positions:

• chr15-48203311-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000417307.3(CTXN2):​c.*1765C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.843 in 167,026 control chromosomes in the GnomAD database, including 63,613 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.83 (56211 hom., cov: 31)
  • Exomes 𝑓: 1.0 (7402 hom.)
• Consequence: CTXN2 ENST00000417307.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349

Genes affected

CTXN2 (HGNC:31109): (cortexin 2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC12A1 (HGNC:10910): (solute carrier family 12 member 1) This gene encodes a kidney-specific sodium-potassium-chloride cotransporter that is expressed on the luminal membrane of renal epithelial cells of the thick ascending limb of Henle's loop and the macula densa. It plays a key role in concentrating urine and accounts for most of the NaCl resorption. It is sensitive to such diuretics as furosemide and bumetanide. Some Bartter-like syndromes result from defects in this gene. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional splice variants have been described but their biological validity in humans has not been experimentally proven.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTXN2	NM_001145668.2	c.*1765C>T		3_prime_UTR_variant	2/2	ENST00000417307.3	NP_001139140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTXN2	ENST00000417307.3	c.*1765C>T		3_prime_UTR_variant	2/2	1	NM_001145668.2	ENSP00000406145	P1

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125894 AN: 151990 Hom.: 56201 Cov.: 31

Gnomad AFR AF: 0.477

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.922

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.872

GnomAD4 exome AF: 0.996 AC: 14860 AN: 14918 Hom.: 7402 Cov.: 0 AF XY: 0.996 AC XY: 7066 AN XY: 7094

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.833

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.997

Gnomad4 NFE exome AF: 0.981

Gnomad4 OTH exome AF: 0.989

GnomAD4 genome AF: 0.828 AC: 125939 AN: 152108 Hom.: 56211 Cov.: 31 AF XY: 0.829 AC XY: 61675 AN XY: 74366

Gnomad4 AFR AF: 0.476

Gnomad4 AMR AF: 0.922

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.846

Gnomad4 FIN AF: 0.998

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.864

Alfa AF: 0.868 Hom.: 23731

Bravo AF: 0.807

Asia WGS AF: 0.634 AC: 2210 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.36

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: rs1320052; hg19: chr15-48495508; COSMIC: COSV57711825; COSMIC: COSV57711825;