rs594709

Positions:

• chr6-160134722-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.839+597G>A		intron_variant		ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.839+597G>A		intron_variant			NP_694857.1
SLC22A1	XM_005267103.3	c.839+597G>A		intron_variant			XP_005267160.1
SLC22A1	XM_006715552.3	c.839+597G>A		intron_variant			XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.839+597G>A		intron_variant		1	NM_003057.3	ENSP00000355930	P1

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

Gnomad4 AFR AF: 0.694

Gnomad4 AMR AF: 0.732

Gnomad4 ASJ AF: 0.666

Gnomad4 EAS AF: 0.731

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.597

Gnomad4 OTH AF: 0.668

Alfa AF: 0.628 Hom.: 8616

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
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs594709; hg19: chr6-160555754;