rs4149183

Positions:

• chr11-62998397-A-G
• chr11-62998397-A-T

Variant summary

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

The NM_004254.4(SLC22A8):​c.761+524T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,892 control chromosomes in the GnomAD database, including 5,860 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 (5860 hom., cov: 32)
• Consequence: SLC22A8 NM_004254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A8	NM_004254.4	c.761+524T>C		intron_variant		ENST00000336232.7	NP_004245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A8	ENST00000336232.7	c.761+524T>C		intron_variant		1	NM_004254.4	ENSP00000337335	P1

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39897 AN: 151774 Hom.: 5825 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.263 AC: 39979 AN: 151892 Hom.: 5860 Cov.: 32 AF XY: 0.262 AC XY: 19425 AN XY: 74232

Gnomad4 AFR AF: 0.378

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.242

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.253

Alfa AF: 0.227 Hom.: 8286

Bravo AF: 0.265

Asia WGS AF: 0.236 AC: 820 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.1
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4149183; hg19: chr11-62765869;