rs3737088

chr6-160132133-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.516-99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0534 in 1,258,238 control chromosomes in the GnomAD database, including 2,424 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 0.075 (635 hom., cov: 32)
  • Exomes 𝑓: 0.050 (1789 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.48

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 (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A1	NM_003057.3	c.516-99C>T		intron_variant		ENST00000366963.9
SLC22A1	NM_153187.2	c.516-99C>T		intron_variant
SLC22A1	XM_005267103.3	c.516-99C>T		intron_variant
SLC22A1	XM_006715552.3	c.516-99C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9	c.516-99C>T		intron_variant		1	NM_003057.3	P1

Frequencies

GnomAD3 genomes AF: 0.0752 AC: 11438 AN: 152072 Hom.: 634 Cov.: 32

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0719

Gnomad ASJ AF: 0.0825

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.0700

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0438

Gnomad OTH AF: 0.0797

GnomAD4 exome AF: 0.0504 AC: 55736 AN: 1106048 Hom.: 1789 AF XY: 0.0507 AC XY: 27873 AN XY: 549238

Gnomad4 AFR exome AF: 0.154

Gnomad4 AMR exome AF: 0.0544

Gnomad4 ASJ exome AF: 0.0808

Gnomad4 EAS exome AF: 0.0358

Gnomad4 SAS exome AF: 0.0685

Gnomad4 FIN exome AF: 0.0257

Gnomad4 NFE exome AF: 0.0463

Gnomad4 OTH exome AF: 0.0623

GnomAD4 genome AF: 0.0753 AC: 11454 AN: 152190 Hom.: 635 Cov.: 32 AF XY: 0.0730 AC XY: 5435 AN XY: 74408

Gnomad4 AFR AF: 0.148

Gnomad4 AMR AF: 0.0718

Gnomad4 ASJ AF: 0.0825

Gnomad4 EAS AF: 0.0334

Gnomad4 SAS AF: 0.0694

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.0438

Gnomad4 OTH AF: 0.0807

Alfa AF: 0.0731 Hom.: 90

Bravo AF: 0.0824

Asia WGS AF: 0.0600 AC: 208 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	0.034
Dann	Benign	0.48

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: rs3737088; hg19: chr6-160553165;