rs2413890

Variant names:

• chr15-48234165-G-T
• rs2413890
• NM_000338.3:c.1088-712G>T

Variant summary

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

The NM_000338.3(SLC12A1):​c.1088-712G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,040 control chromosomes in the GnomAD database, including 32,946 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 0.61 (32946 hom., cov: 31)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821
• Publications: 0 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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000338.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A1	NM_000338.3	MANE Select	c.1088-712G>T		intron	N/A	NP_000329.2	Q13621-1
	SLC12A1	NM_001184832.2		c.1088-712G>T		intron	N/A	NP_001171761.1	Q13621-3
	SLC12A1	NM_001384136.1		c.1088-712G>T		intron	N/A	NP_001371065.1	A0A8I5KSK6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A1	ENST00000380993.8	TSL:5 MANE Select	c.1088-712G>T		intron	N/A	ENSP00000370381.3	Q13621-1
	SLC12A1	ENST00000330289.10	TSL:1	c.1088-712G>T		intron	N/A	ENSP00000331550.6	Q8IUN5
	SLC12A1	ENST00000558252.5	TSL:1	n.5211-712G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.613 AC: 93081 AN: 151922 Hom.: 32957 Cov.: 31

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.829

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.769

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.689

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.652

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

GnomAD4 genome AF: 0.612 AC: 93078 AN: 152040 Hom.: 32946 Cov.: 31 AF XY: 0.614 AC XY: 45663 AN XY: 74310

African (AFR) AF: 0.260 AC: 10764 AN: 41438

American (AMR) AF: 0.673 AC: 10284 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.769 AC: 2671 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1373 AN: 5158

South Asian (SAS) AF: 0.690 AC: 3329 AN: 4824

European-Finnish (FIN) AF: 0.793 AC: 8396 AN: 10584

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53913 AN: 67976

Other (OTH) AF: 0.644 AC: 1360 AN: 2112

Alfa AF: 0.668 Hom.: 4777

Bravo AF: 0.589

Asia WGS AF: 0.461 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.53
PhyloP100		-0.82
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: rs2413890; hg19: chr15-48526362;