15-48179327-A-C

Variant names:

• chr15-48179327-A-C
• rs11070627
• ENST00000647232.1:c.-301+681A>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001370415.1(CTXN2):​c.-58+681A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 30)
• Consequence: CTXN2 NM_001370415.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872

Genes affected

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]

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTXN2	NM_001370415.1	c.-58+681A>C		intron_variant	Intron 1 of 1		NP_001357344.1
CTXN2	XM_017022178.2	c.-172+681A>C		intron_variant	Intron 1 of 2		XP_016877667.1
CTXN2	XM_047432494.1	c.-455+681A>C		intron_variant	Intron 1 of 2		XP_047288450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A1	ENST00000647232.1	c.-301+681A>C		intron_variant	Intron 1 of 27			ENSP00000493875.1
CTXN2	ENST00000644354.1	c.-455+927A>C		intron_variant	Intron 1 of 2			ENSP00000495988.1
CTXN2	ENST00000645050.1	c.-58+681A>C		intron_variant	Intron 1 of 1			ENSP00000495979.1

Frequencies

GnomAD3 genomes Cov.: 30

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

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.41
DANN	Benign	0.39

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11070627; hg19: chr15-48471524;