rs4709400

Positions:

• chr6-160122578-C-G
• chr6-160122578-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003057.3(SLC22A1):​c.411+232C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 603,936 control chromosomes in the GnomAD database, including 17,801 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 0.29 (7021 hom., cov: 32)
  • Exomes 𝑓: 0.21 (10780 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

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=-1.05).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.411+232C>G		intron_variant		ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.411+232C>G		intron_variant			NP_694857.1
SLC22A1	XM_005267103.3	c.411+232C>G		intron_variant			XP_005267160.1
SLC22A1	XM_006715552.3	c.411+232C>G		intron_variant			XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.411+232C>G		intron_variant		1	NM_003057.3	ENSP00000355930	P1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44172 AN: 151774 Hom.: 7001 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.315

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.211 AC: 95216 AN: 452044 Hom.: 10780 AF XY: 0.211 AC XY: 44824 AN XY: 212730

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.307

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.505

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.291 AC: 44245 AN: 151892 Hom.: 7021 Cov.: 32 AF XY: 0.292 AC XY: 21702 AN XY: 74220

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.315

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.273

Alfa AF: 0.121 Hom.: 188

Bravo AF: 0.307

Asia WGS AF: 0.405 AC: 1409 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.072
DANN	Benign	0.30

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: rs4709400; hg19: chr6-160543610;