rs4551716

Variant names:

• chr11-26673295-C-T
• rs4551716
• NM_178498.4:c.1707+107G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178498.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A12	NM_178498.4	MANE Select	c.1707+107G>A		intron	N/A	NP_848593.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A12	ENST00000396005.8	TSL:1 MANE Select	c.1707+107G>A		intron	N/A	ENSP00000379326.3
	SLC5A12	ENST00000527405.5	TSL:2	n.*313+107G>A		intron	N/A	ENSP00000436011.1

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

African (AFR) AF: 0.435 AC: 10056 AN: 23120

American (AMR) AF: 0.289 AC: 5485 AN: 19002

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 8146 AN: 15820

East Asian (EAS) AF: 0.373 AC: 11691 AN: 31336

South Asian (SAS) AF: 0.503 AC: 19949 AN: 39692

European-Finnish (FIN) AF: 0.412 AC: 16233 AN: 39354

Middle Eastern (MID) AF: 0.477 AC: 2183 AN: 4576

European-Non Finnish (NFE) AF: 0.493 AC: 425791 AN: 863312

Other (OTH) AF: 0.472 AC: 21149 AN: 44826

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

African (AFR) AF: 0.438 AC: 18185 AN: 41476

American (AMR) AF: 0.364 AC: 5554 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1815 AN: 3468

East Asian (EAS) AF: 0.354 AC: 1829 AN: 5168

South Asian (SAS) AF: 0.502 AC: 2426 AN: 4828

European-Finnish (FIN) AF: 0.397 AC: 4190 AN: 10556

Middle Eastern (MID) AF: 0.551 AC: 162 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34219 AN: 67966

Other (OTH) AF: 0.454 AC: 959 AN: 2112

Alfa AF: 0.484 Hom.: 29840

Bravo AF: 0.453

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.48
PhyloP100		-0.35
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: rs4551716; hg19: chr11-26694842; COSMIC: COSV68450548;