12-101200304-G-A

Variant names:

• chr12-101200304-G-A
• rs189488
• NM_145913.5:c.469+1860C>T

Variant summary

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

The NM_145913.5(SLC5A8):​c.469+1860C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,640 control chromosomes in the GnomAD database, including 17,191 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 0.47 (17191 hom., cov: 31)
• Consequence: SLC5A8 NM_145913.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356
• Publications: 5 publications found

Genes affected

SLC5A8 (HGNC:19119): (solute carrier family 5 member 8) SLC5A8 has been shown to transport iodide by a passive mechanism (Rodriguez et al., 2002 [PubMed 12107270]) and monocarboxylates and short-chain fatty acids by a sodium-coupled mechanism (Gopal et al., 2004 [PubMed 15322102]). In kidney, SLC5A8 functions as a high-affinity sodium-coupled lactate transporter involved in reabsorption of lactate and maintenance of blood lactate levels (Thangaraju et al., 2006 [PubMed 16873376]).[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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145913.5. 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
	SLC5A8	NM_145913.5	MANE Select	c.469+1860C>T		intron	N/A	NP_666018.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A8	ENST00000536262.3	TSL:1 MANE Select	c.469+1860C>T		intron	N/A	ENSP00000445340.2

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71442 AN: 151522 Hom.: 17168 Cov.: 31

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.645

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.472 AC: 71505 AN: 151640 Hom.: 17191 Cov.: 31 AF XY: 0.475 AC XY: 35165 AN XY: 74090

African (AFR) AF: 0.546 AC: 22596 AN: 41364

American (AMR) AF: 0.419 AC: 6376 AN: 15210

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1619 AN: 3470

East Asian (EAS) AF: 0.645 AC: 3328 AN: 5160

South Asian (SAS) AF: 0.418 AC: 2016 AN: 4818

European-Finnish (FIN) AF: 0.509 AC: 5357 AN: 10520

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28730 AN: 67792

Other (OTH) AF: 0.461 AC: 970 AN: 2104

Alfa AF: 0.442 Hom.: 29082

Bravo AF: 0.472

Asia WGS AF: 0.522 AC: 1811 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.82
DANN	Benign	0.67
PhyloP100		-0.36
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: rs189488; hg19: chr12-101594082;