rs4963326

Variant names:

• chr11-63013105-A-G
• rs4963326
• NM_004254.4:c.333+1521T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-63013105-A-G
• chr11-63013105-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004254.4(SLC22A8):​c.333+1521T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 151,910 control chromosomes in the GnomAD database, including 25,386 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 0.57 (25386 hom., cov: 31)
• Consequence: SLC22A8 NM_004254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.865
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 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.333+1521T>C		intron	N/A	NP_004245.2
	SLC22A8	NM_001184732.2		c.333+1521T>C		intron	N/A	NP_001171661.1	Q8TCC7-1
	SLC22A8	NM_001184733.2		c.60+1521T>C		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.333+1521T>C		intron	N/A	ENSP00000337335.2	Q8TCC7-1
	SLC22A8	ENST00000430500.6	TSL:1	c.333+1521T>C		intron	N/A	ENSP00000398548.2	Q8TCC7-1
	SLC22A8	ENST00000311438.12	TSL:1	c.333+1521T>C		intron	N/A	ENSP00000311463.8	H7BXN9

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86889 AN: 151792 Hom.: 25383 Cov.: 31

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.769

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.572 AC: 86915 AN: 151910 Hom.: 25386 Cov.: 31 AF XY: 0.571 AC XY: 42414 AN XY: 74220

African (AFR) AF: 0.458 AC: 18961 AN: 41368

American (AMR) AF: 0.536 AC: 8185 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1899 AN: 3468

East Asian (EAS) AF: 0.713 AC: 3677 AN: 5160

South Asian (SAS) AF: 0.575 AC: 2765 AN: 4812

European-Finnish (FIN) AF: 0.666 AC: 7033 AN: 10556

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42260 AN: 67968

Other (OTH) AF: 0.588 AC: 1240 AN: 2110

Alfa AF: 0.598 Hom.: 34452

Bravo AF: 0.561

Asia WGS AF: 0.674 AC: 2345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.014
DANN	Benign	0.37
PhyloP100		-0.86
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: rs4963326; hg19: chr11-62780577;