chr15-48179327-A-T

Variant names:

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

Variant summary

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

The ENST00000647232.1(SLC12A1):​c.-301+681A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 151,962 control chromosomes in the GnomAD database, including 56,193 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 (56193 hom., cov: 30)
• Consequence: SLC12A1 ENST00000647232.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• 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_001370415.1	c.-58+681A>T		intron_variant	Intron 1 of 1		NP_001357344.1
CTXN2	XM_017022178.2	c.-172+681A>T		intron_variant	Intron 1 of 2		XP_016877667.1
CTXN2	XM_047432494.1	c.-455+681A>T		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>T		intron_variant	Intron 1 of 27			ENSP00000493875.1
CTXN2	ENST00000644354.1	c.-455+927A>T		intron_variant	Intron 1 of 2			ENSP00000495988.1
CTXN2	ENST00000645050.1	c.-58+681A>T		intron_variant	Intron 1 of 1			ENSP00000495979.1

Frequencies

GnomAD3 genomes AF: 0.829 AC: 125809 AN: 151844 Hom.: 56184 Cov.: 30

Gnomad AFR AF: 0.476

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.987

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.828 AC: 125851 AN: 151962 Hom.: 56193 Cov.: 30 AF XY: 0.830 AC XY: 61663 AN XY: 74298

African (AFR) AF: 0.476 AC: 19677 AN: 41324

American (AMR) AF: 0.922 AC: 14068 AN: 15266

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3471 AN: 3472

East Asian (EAS) AF: 0.595 AC: 3070 AN: 5164

South Asian (SAS) AF: 0.847 AC: 4070 AN: 4806

European-Finnish (FIN) AF: 0.998 AC: 10571 AN: 10596

Middle Eastern (MID) AF: 0.986 AC: 290 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67903 AN: 68022

Other (OTH) AF: 0.864 AC: 1819 AN: 2106

Alfa AF: 0.905 Hom.: 8090

Bravo AF: 0.807

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	-0.85
CADD	Benign	0.41
DANN	Benign	0.50
PhyloP100		-0.87

Splicing

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

Other links and lift over

dbSNP: rs11070627; hg19: chr15-48471524;