rs953894

Variant names:

• chr11-62994950-C-T
• rs953894
• NM_004254.4:c.1002-194G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ENSG00000301851 (HGNC:):

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004254.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A8	NM_004254.4	MANE Select	c.1002-194G>A		intron	N/A	NP_004245.2
	SLC22A8	NM_001184732.2		c.1002-194G>A		intron	N/A	NP_001171661.1	Q8TCC7-1
	SLC22A8	NM_001184733.2		c.729-194G>A		intron	N/A	NP_001171662.1	Q8TCC7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A8	ENST00000336232.7	TSL:1 MANE Select	c.1002-194G>A		intron	N/A	ENSP00000337335.2	Q8TCC7-1
	SLC22A8	ENST00000430500.6	TSL:1	c.1002-194G>A		intron	N/A	ENSP00000398548.2	Q8TCC7-1
	SLC22A8	ENST00000311438.12	TSL:1	c.1002-194G>A		intron	N/A	ENSP00000311463.8	H7BXN9

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

African (AFR) AF: 0.376 AC: 5054 AN: 13426

American (AMR) AF: 0.128 AC: 3267 AN: 25550

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 2711 AN: 14660

East Asian (EAS) AF: 0.335 AC: 10335 AN: 30832

South Asian (SAS) AF: 0.156 AC: 7773 AN: 49714

European-Finnish (FIN) AF: 0.241 AC: 7204 AN: 29902

Middle Eastern (MID) AF: 0.258 AC: 524 AN: 2028

European-Non Finnish (NFE) AF: 0.225 AC: 61997 AN: 275536

Other (OTH) AF: 0.227 AC: 6049 AN: 26676

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

African (AFR) AF: 0.377 AC: 15635 AN: 41454

American (AMR) AF: 0.172 AC: 2627 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3464

East Asian (EAS) AF: 0.327 AC: 1690 AN: 5170

South Asian (SAS) AF: 0.166 AC: 800 AN: 4812

European-Finnish (FIN) AF: 0.241 AC: 2549 AN: 10584

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15081 AN: 67970

Other (OTH) AF: 0.253 AC: 533 AN: 2110

Alfa AF: 0.228 Hom.: 7193

Bravo AF: 0.264

Asia WGS AF: 0.237 AC: 824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.47
PhyloP100		-1.1
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: rs953894; hg19: chr11-62762422;