rs3805668

Variant names:

• chr5-132310895-G-A
• rs3805668
• NM_003059.3:c.394-1266G>A

Variant summary

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

The NM_003059.3(SLC22A4):​c.394-1266G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0732 in 152,182 control chromosomes in the GnomAD database, including 543 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 0.073 (543 hom., cov: 32)
• Consequence: SLC22A4 NM_003059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 6 publications found

Genes affected

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -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 = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.394-1266G>A		intron_variant	Intron 1 of 9	ENST00000200652.4	NP_003050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.394-1266G>A		intron_variant	Intron 1 of 9	1	NM_003059.3	ENSP00000200652.3
SLC22A4	ENST00000491257.1	n.198-1266G>A		intron_variant	Intron 1 of 3	4

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11138 AN: 152064 Hom.: 546 Cov.: 32

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0484

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.0648

Gnomad FIN AF: 0.0752

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0731

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

GnomAD4 genome AF: 0.0732 AC: 11137 AN: 152182 Hom.: 543 Cov.: 32 AF XY: 0.0724 AC XY: 5384 AN XY: 74392

African (AFR) AF: 0.0493 AC: 2047 AN: 41522

American (AMR) AF: 0.0483 AC: 739 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3468

East Asian (EAS) AF: 0.268 AC: 1386 AN: 5172

South Asian (SAS) AF: 0.0647 AC: 312 AN: 4824

European-Finnish (FIN) AF: 0.0752 AC: 796 AN: 10586

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0766 AC: 5208 AN: 67994

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.0736 Hom.: 562

Bravo AF: 0.0702

Asia WGS AF: 0.121 AC: 422 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	1.9
DANN	Benign	0.50
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3805668; hg19: chr5-131646588;