rs594709

Variant names:

• chr6-160134722-G-A
• rs594709
• NM_003057.3:c.839+597G>A

Variant summary

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

The NM_003057.3(SLC22A1):​c.839+597G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.643 in 152,016 control chromosomes in the GnomAD database, including 31,644 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 0.64 (31644 hom., cov: 35)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.02
• Publications: 34 publications found

Genes affected

SLC22A1 (HGNC:10963): (solute carrier family 22 member 1) 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. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.839+597G>A		intron_variant	Intron 4 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.839+597G>A		intron_variant	Intron 4 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.839+597G>A		intron_variant	Intron 4 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.839+597G>A		intron_variant	Intron 4 of 11		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.839+597G>A		intron_variant	Intron 4 of 10	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97623 AN: 151900 Hom.: 31604 Cov.: 35

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.732

Gnomad ASJ AF: 0.666

Gnomad EAS AF: 0.731

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.737

Gnomad NFE AF: 0.597

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.643 AC: 97721 AN: 152016 Hom.: 31644 Cov.: 35 AF XY: 0.643 AC XY: 47813 AN XY: 74312

African (AFR) AF: 0.694 AC: 28703 AN: 41382

American (AMR) AF: 0.732 AC: 11198 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 2311 AN: 3470

East Asian (EAS) AF: 0.731 AC: 3785 AN: 5176

South Asian (SAS) AF: 0.622 AC: 3005 AN: 4828

European-Finnish (FIN) AF: 0.561 AC: 5936 AN: 10586

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.597 AC: 40595 AN: 67970

Other (OTH) AF: 0.668 AC: 1409 AN: 2108

Alfa AF: 0.628 Hom.: 19432

Bravo AF: 0.662

Asia WGS AF: 0.676 AC: 2348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.059
DANN	Benign	0.46
PhyloP100		-4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs594709; hg19: chr6-160555754;