chr15-48231070-A-G

Variant names:

• chr15-48231070-A-G
• rs12904216
• NM_000338.3:c.975+567A>G

Variant summary

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

The NM_000338.3(SLC12A1):​c.975+567A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,136 control chromosomes in the GnomAD database, including 33,991 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 0.63 (33991 hom., cov: 32)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 9 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):

• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A1	NM_000338.3	c.975+567A>G		intron_variant	Intron 7 of 26	ENST00000380993.8	NP_000329.2
SLC12A1	NM_001184832.2	c.975+567A>G		intron_variant	Intron 7 of 26		NP_001171761.1
SLC12A1	NM_001384136.1	c.975+567A>G		intron_variant	Intron 7 of 26		NP_001371065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A1	ENST00000380993.8	c.975+567A>G		intron_variant	Intron 7 of 26	5	NM_000338.3	ENSP00000370381.3

Frequencies

GnomAD3 genomes AF: 0.626 AC: 95213 AN: 152016 Hom.: 34006 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.681

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.794

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.626 AC: 95208 AN: 152136 Hom.: 33991 Cov.: 32 AF XY: 0.629 AC XY: 46756 AN XY: 74356

African (AFR) AF: 0.280 AC: 11611 AN: 41488

American (AMR) AF: 0.680 AC: 10389 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2690 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1714 AN: 5178

South Asian (SAS) AF: 0.743 AC: 3579 AN: 4814

European-Finnish (FIN) AF: 0.794 AC: 8401 AN: 10576

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54438 AN: 68006

Other (OTH) AF: 0.659 AC: 1394 AN: 2116

Alfa AF: 0.740 Hom.: 54226

Bravo AF: 0.602

Asia WGS AF: 0.527 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.047
DANN	Benign	0.29
PhyloP100		-2.1
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: rs12904216; hg19: chr15-48523267;