rs3805665

Variant names:

• chr5-132309025-G-A
• rs3805665
• NM_003059.3:c.394-3136G>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.394-3136G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0729 in 152,254 control chromosomes in the GnomAD database, including 540 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 (540 hom., cov: 32)
• Consequence: SLC22A4 NM_003059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.41
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003059.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A4	NM_003059.3	MANE Select	c.394-3136G>A		intron	N/A	NP_003050.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A4	ENST00000200652.4	TSL:1 MANE Select	c.394-3136G>A		intron	N/A	ENSP00000200652.3
	SLC22A4	ENST00000491257.1	TSL:4	n.198-3136G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0730 AC: 11104 AN: 152136 Hom.: 543 Cov.: 32

Gnomad AFR AF: 0.0492

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0465

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.0649

Gnomad FIN AF: 0.0751

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0765

Gnomad OTH AF: 0.0727

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

GnomAD4 genome AF: 0.0729 AC: 11104 AN: 152254 Hom.: 540 Cov.: 32 AF XY: 0.0721 AC XY: 5370 AN XY: 74436

African (AFR) AF: 0.0493 AC: 2048 AN: 41548

American (AMR) AF: 0.0465 AC: 711 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 376 AN: 3470

East Asian (EAS) AF: 0.268 AC: 1387 AN: 5174

South Asian (SAS) AF: 0.0648 AC: 313 AN: 4832

European-Finnish (FIN) AF: 0.0751 AC: 797 AN: 10606

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

European-Non Finnish (NFE) AF: 0.0765 AC: 5200 AN: 68000

Other (OTH) AF: 0.0729 AC: 154 AN: 2112

Alfa AF: 0.0732 Hom.: 729

Bravo AF: 0.0698

Asia WGS AF: 0.121 AC: 422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.075
DANN	Benign	0.44
PhyloP100		-1.4
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: rs3805665; hg19: chr5-131644718;