rs2187383

Positions:

• chr11-63008426-A-C
• chr11-63008426-A-G
• chr11-63008426-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.333+6200T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.648 in 152,048 control chromosomes in the GnomAD database, including 32,204 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 0.65 (32204 hom., cov: 31)
• Consequence: SLC22A8 NM_004254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.75 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A8	NM_004254.4	c.333+6200T>G		intron_variant		ENST00000336232.7
SLC22A8	NM_001184732.2	c.333+6200T>G		intron_variant
SLC22A8	NM_001184733.2	c.60+6200T>G		intron_variant
SLC22A8	NM_001184736.2	c.-37+7303T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A8	ENST00000336232.7	c.333+6200T>G		intron_variant		1	NM_004254.4	P1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98410 AN: 151930 Hom.: 32147 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.769

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.675

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.648 AC: 98529 AN: 152048 Hom.: 32204 Cov.: 31 AF XY: 0.653 AC XY: 48547 AN XY: 74302

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.647

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.591

Gnomad4 OTH AF: 0.663

Alfa AF: 0.606 Hom.: 36069

Bravo AF: 0.649

Asia WGS AF: 0.754 AC: 2620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.3
DANN	Benign	0.75

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: rs2187383; hg19: chr11-62775898;