chr15-48207506-C-T

Position:

• chr15-48207506-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000338.3(SLC12A1):​c.-186-28C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 395,452 control chromosomes in the GnomAD database, including 3,140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (1211 hom., cov: 32)
  • Exomes 𝑓: 0.047 (1929 hom.)
• Consequence: SLC12A1 NM_000338.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0450

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 15-48207506-C-T is Benign according to our data. Variant chr15-48207506-C-T is described in ClinVar as [Benign]. Clinvar id is 1276462.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A1	NM_000338.3	c.-186-28C>T		intron_variant		ENST00000380993.8	NP_000329.2
SLC12A1	NM_001184832.2	c.-186-28C>T		intron_variant			NP_001171761.1
SLC12A1	NM_001384136.1	c.-186-28C>T		intron_variant			NP_001371065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A1	ENST00000380993.8	c.-186-28C>T		intron_variant		5	NM_000338.3	ENSP00000370381	A1

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11357 AN: 152052 Hom.: 1204 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0507

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.408

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.0689

GnomAD4 exome AF: 0.0466 AC: 11335 AN: 243282 Hom.: 1929 Cov.: 3 AF XY: 0.0452 AC XY: 5577 AN XY: 123432

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.0482

Gnomad4 ASJ exome AF: 0.000232

Gnomad4 EAS exome AF: 0.403

Gnomad4 SAS exome AF: 0.0808

Gnomad4 FIN exome AF: 0.00227

Gnomad4 NFE exome AF: 0.00169

Gnomad4 OTH exome AF: 0.0490

GnomAD4 genome AF: 0.0748 AC: 11377 AN: 152170 Hom.: 1211 Cov.: 32 AF XY: 0.0771 AC XY: 5737 AN XY: 74430

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0507

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.00141

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.00119 Hom.: 0

Bravo AF: 0.0829

Asia WGS AF: 0.311 AC: 1077 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 26, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	5.1
DANN	Benign	0.70

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: rs16960656; hg19: chr15-48499703;