15-48229719-T-C

Position:

• chr15-48229719-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000338.3(SLC12A1):​c.864+391T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 152,270 control chromosomes in the GnomAD database, including 66,679 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 0.93 (66679 hom., cov: 33)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

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]

LOC128966560 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A1	NM_000338.3	c.864+391T>C		intron_variant		ENST00000380993.8	NP_000329.2
SLC12A1	NM_001184832.2	c.864+391T>C		intron_variant			NP_001171761.1
SLC12A1	NM_001384136.1	c.864+391T>C		intron_variant			NP_001371065.1
LOC128966560	XR_932204.4	n.222+237A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A1	ENST00000380993.8	c.864+391T>C		intron_variant		5	NM_000338.3	ENSP00000370381.3

Frequencies

GnomAD3 genomes AF: 0.932 AC: 141771 AN: 152152 Hom.: 66640 Cov.: 33

Gnomad AFR AF: 0.834

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.956

Gnomad ASJ AF: 0.998

Gnomad EAS AF: 0.651

Gnomad SAS AF: 0.952

Gnomad FIN AF: 0.993

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.991

Gnomad OTH AF: 0.946

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

GnomAD4 genome AF: 0.932 AC: 141867 AN: 152270 Hom.: 66679 Cov.: 33 AF XY: 0.930 AC XY: 69269 AN XY: 74448

Gnomad4 AFR AF: 0.834

Gnomad4 AMR AF: 0.956

Gnomad4 ASJ AF: 0.998

Gnomad4 EAS AF: 0.652

Gnomad4 SAS AF: 0.952

Gnomad4 FIN AF: 0.993

Gnomad4 NFE AF: 0.991

Gnomad4 OTH AF: 0.947

Alfa AF: 0.983 Hom.: 104562

Bravo AF: 0.925

Asia WGS AF: 0.828 AC: 2876 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	11
DANN	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs3784614; hg19: chr15-48521916;