rs12913316

chr15-48195657-C-T

Variant summary

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

The NM_001145668.2(CTXN2):c.-58+3804C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.816 in 152,162 control chromosomes in the GnomAD database, including 55,426 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 0.82 (55426 hom., cov: 33)
• Consequence: CTXN2 NM_001145668.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541

Genes affected

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

(HGNC:):

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	UniProt
CTXN2	NM_001145668.2	c.-58+3804C>T		intron_variant		ENST00000417307.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CTXN2	ENST00000417307.3	c.-58+3804C>T		intron_variant		1	NM_001145668.2	P1
	ENST00000559875.1	n.446-3217G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.816 AC: 124068 AN: 152044 Hom.: 55418 Cov.: 33

Gnomad AFR AF: 0.433

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.864

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

GnomAD4 genome AF: 0.816 AC: 124104 AN: 152162 Hom.: 55426 Cov.: 33 AF XY: 0.817 AC XY: 60841 AN XY: 74426

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.918

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 0.599

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.998

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.856

Alfa AF: 0.898 Hom.: 8030

Bravo AF: 0.793

Asia WGS AF: 0.637 AC: 2222 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	2.4
Dann	Benign	0.61

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: rs12913316; hg19: chr15-48487854;