rs953894

Positions:

• chr11-62994950-C-T

Variant summary

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

The NM_004254.4(SLC22A8):​c.1002-194G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 620,388 control chromosomes in the GnomAD database, including 18,333 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 0.26 (5842 hom., cov: 32)
  • Exomes 𝑓: 0.22 (12491 hom.)
• Consequence: SLC22A8 NM_004254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

Genes affected

SLC22A8 (HGNC:10972): (solute carrier family 22 member 8) This gene encodes a protein involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]

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 (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A8	NM_004254.4	c.1002-194G>A		intron_variant		ENST00000336232.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A8	ENST00000336232.7	c.1002-194G>A		intron_variant		1	NM_004254.4	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39840 AN: 151946 Hom.: 5804 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.326

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.224 AC: 104914 AN: 468324 Hom.: 12491 Cov.: 4 AF XY: 0.219 AC XY: 54567 AN XY: 248654

Gnomad4 AFR exome AF: 0.376

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.335

Gnomad4 SAS exome AF: 0.156

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.263 AC: 39925 AN: 152064 Hom.: 5842 Cov.: 32 AF XY: 0.261 AC XY: 19398 AN XY: 74338

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.253

Alfa AF: 0.224 Hom.: 5476

Bravo AF: 0.264

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.47

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: rs953894; hg19: chr11-62762422;