rs4963326

Positions:

• chr11-63013105-A-G
• chr11-63013105-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+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

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A8	NM_004254.4	c.333+1521T>C		intron_variant		ENST00000336232.7
SLC22A8	NM_001184732.2	c.333+1521T>C		intron_variant
SLC22A8	NM_001184733.2	c.60+1521T>C		intron_variant
SLC22A8	NM_001184736.2	c.-37+2624T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A8	ENST00000336232.7	c.333+1521T>C		intron_variant		1	NM_004254.4	P1

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

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.713

Gnomad4 SAS AF: 0.575

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.588

Alfa AF: 0.604 Hom.: 26586

Bravo AF: 0.561

Asia WGS AF: 0.674 AC: 2345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.014
DANN	Benign	0.37

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: rs4963326; hg19: chr11-62780577;