rs4551716

chr11-26673295-C-T

Variant summary

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

The NM_178498.4(SLC5A12):c.1707+107G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 1,233,078 control chromosomes in the GnomAD database, including 143,048 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 0.46 (16300 hom., cov: 33)
  • Exomes 𝑓: 0.48 (126748 hom.)
• Consequence: SLC5A12 NM_178498.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353

Genes affected

SLC5A12 (HGNC:28750): (solute carrier family 5 member 12) Normal blood lactate is maintained at about 1.5 mM, and little filtered lactate is excreted in urine. Reabsorption of lactate is mediated by the low-affinity Na(+)-coupled lactate transporter SLC5A12 in the initial part of the proximal tubule and by the high-affinity Na(+)-coupled lactate transporter SLC5A8 (MIM 608044) in the distal proximal tubule (Gopal et al., 2007 [PubMed 17692818]).[supplied by OMIM, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A12	NM_178498.4	c.1707+107G>A		intron_variant		ENST00000396005.8
SLC5A12	XM_006718155.4	c.1374+107G>A		intron_variant
SLC5A12	XM_011519920.3	c.1143+107G>A		intron_variant
SLC5A12	XM_017017244.2	c.1143+107G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A12	ENST00000396005.8	c.1707+107G>A		intron_variant		1	NM_178498.4	P1
SLC5A12	ENST00000527405.5	c.*313+107G>A		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69730 AN: 151924 Hom.: 16286 Cov.: 33

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.454

GnomAD4 exome AF: 0.482 AC: 520683 AN: 1081038 Hom.: 126748 AF XY: 0.483 AC XY: 255398 AN XY: 528570

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.289

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.373

Gnomad4 SAS exome AF: 0.503

Gnomad4 FIN exome AF: 0.412

Gnomad4 NFE exome AF: 0.493

Gnomad4 OTH exome AF: 0.472

GnomAD4 genome AF: 0.459 AC: 69778 AN: 152040 Hom.: 16300 Cov.: 33 AF XY: 0.454 AC XY: 33750 AN XY: 74292

Gnomad4 AFR AF: 0.438

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.354

Gnomad4 SAS AF: 0.502

Gnomad4 FIN AF: 0.397

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.454

Alfa AF: 0.488 Hom.: 23903

Bravo AF: 0.453

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.25
Dann	Benign	0.48

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: rs4551716; hg19: chr11-26694842; COSMIC: COSV68450548;