NM_001145668.2:c.*1765C>T

Variant names:

• chr15-48203311-C-T
• rs1320052
• NM_001145668.2:c.*1765C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145668.2(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 NM_001145668.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 7 publications found

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]

SLC12A1 Gene-Disease associations (from GenCC):

• Bartter disease type 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• antenatal Bartter syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CTXN2	NM_001145668.2	c.*1765C>T		3_prime_UTR_variant	Exon 2 of 2	ENST00000417307.3	NP_001139140.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTXN2	ENST00000417307.3	c.*1765C>T		3_prime_UTR_variant	Exon 2 of 2	1	NM_001145668.2	ENSP00000406145.2

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

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 0.833 AC: 5 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 2 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.997 AC: 14651 AN: 14702

Middle Eastern (MID) AF: 1.00 AC: 4 AN: 4

European-Non Finnish (NFE) AF: 0.981 AC: 102 AN: 104

Other (OTH) AF: 0.989 AC: 93 AN: 94

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

African (AFR) AF: 0.476 AC: 19733 AN: 41414

American (AMR) AF: 0.922 AC: 14090 AN: 15278

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3469 AN: 3470

East Asian (EAS) AF: 0.589 AC: 3044 AN: 5170

South Asian (SAS) AF: 0.846 AC: 4071 AN: 4810

European-Finnish (FIN) AF: 0.998 AC: 10593 AN: 10618

Middle Eastern (MID) AF: 0.990 AC: 291 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67910 AN: 68028

Other (OTH) AF: 0.864 AC: 1826 AN: 2114

Alfa AF: 0.871 Hom.: 28727

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
PhyloP100		0.35
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: rs1320052; hg19: chr15-48495508; COSMIC: COSV57711825; COSMIC: COSV57711825;