rs11231299

Positions:

• chr11-63003916-G-A

Variant summary

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

The NM_004254.4(SLC22A8):​c.334-3093C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,132 control chromosomes in the GnomAD database, including 2,148 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 0.15 (2148 hom., cov: 32)
• Consequence: SLC22A8 NM_004254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A8	NM_004254.4	c.334-3093C>T		intron_variant		ENST00000336232.7
SLC22A8	NM_001184732.2	c.334-3093C>T		intron_variant
SLC22A8	NM_001184733.2	c.61-3093C>T		intron_variant
SLC22A8	NM_001184736.2	c.-36-3093C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A8	ENST00000336232.7	c.334-3093C>T		intron_variant		1	NM_004254.4	P1

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23436 AN: 152014 Hom.: 2145 Cov.: 32

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.296

Gnomad SAS AF: 0.0633

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.159

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

GnomAD4 genome AF: 0.154 AC: 23445 AN: 152132 Hom.: 2148 Cov.: 32 AF XY: 0.154 AC XY: 11435 AN XY: 74354

Gnomad4 AFR AF: 0.0753

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.0637

Gnomad4 FIN AF: 0.211

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.161

Alfa AF: 0.186 Hom.: 3919

Bravo AF: 0.149

Asia WGS AF: 0.132 AC: 457 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.7
DANN	Benign	0.83

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: rs11231299; hg19: chr11-62771388;