rs189488

Positions:

• chr12-101200304-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A8	NM_145913.5	c.469+1860C>T		intron_variant		ENST00000536262.3	NP_666018.3
SLC5A8	XM_017018910.3	c.469+1860C>T		intron_variant			XP_016874399.1
SLC5A8	XR_007063055.1	n.859+1860C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A8	ENST00000536262.3	c.469+1860C>T		intron_variant		1	NM_145913.5	ENSP00000445340	P1

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

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.419

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.645

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.461

Alfa AF: 0.433 Hom.: 16547

Bravo AF: 0.472

Asia WGS AF: 0.522 AC: 1811 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.82
DANN	Benign	0.67

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: rs189488; hg19: chr12-101594082;