dbSNP rs1320052: CTXN2:c.*1765C>T (chr15-48203311-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.349

Publications

7 publications found

Variant links:

Genes affected

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

CTXN2 links:

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):

antenatal Bartter syndrome
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Bartter disease type 1
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia

SLC12A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145668.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTXN2	NM_001145668.2	MANE Select	c.*1765C>T	3_prime_UTR	Exon 2 of 2	NP_001139140.1	P0C2S0
CTXN2	NM_001370415.1		c.*1765C>T	3_prime_UTR	Exon 2 of 2	NP_001357344.1	P0C2S0
CTXN2	NM_001370416.1		c.*1765C>T	3_prime_UTR	Exon 2 of 2	NP_001357345.1	P0C2S0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CTXN2	ENST00000417307.3	TSL:1 MANE Select	c.*1765C>T	3_prime_UTR	Exon 2 of 2	ENSP00000406145.2	P0C2S0
CTXN2	ENST00000644354.1		c.*1765C>T	3_prime_UTR	Exon 3 of 3	ENSP00000495988.1	P0C2S0
CTXN2	ENST00000645050.1		c.*1765C>T	3_prime_UTR	Exon 2 of 2	ENSP00000495979.1	P0C2S0

Frequencies

GnomAD3 genomes

AF:

0.828

AC:

125894

AN:

151990

Hom.:

56201

Cov.:

show subpopulations

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.:

AF XY:

0.996

AC XY:

7066

AN XY:

7094

show subpopulations

African (AFR)

AF:

0.750

AC:

AN:

American (AMR)

AF:

0.833

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.997

AC:

14651

AN:

14702

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.981

AC:

102

AN:

104

Other (OTH)

AF:

0.989

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.828

AC:

125939

AN:

152108

Hom.:

56211

Cov.:

AF XY:

0.829

AC XY:

61675

AN XY:

74366

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

707

1413

2120

2826

3533

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

842

1684

2526

3368

4210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.1

(source)

DANN

Benign

0.36

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over