rs3805665

chr5-132309025-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A4	NM_003059.3	c.394-3136G>A		intron_variant		ENST00000200652.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A4	ENST00000200652.4	c.394-3136G>A		intron_variant		1	NM_003059.3	P1
SLC22A4	ENST00000491257.1	n.198-3136G>A		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.0465

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.0648

Gnomad4 FIN AF: 0.0751

Gnomad4 NFE AF: 0.0765

Gnomad4 OTH AF: 0.0729

Alfa AF: 0.0743 Hom.: 585

Bravo AF: 0.0698

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	-0.91
Cadd	Benign	0.075
Dann	Benign	0.44

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: rs3805665; hg19: chr5-131644718;