rs662138

Positions:

• chr6-160143444-C-G

Variant summary

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

The NM_003057.3(SLC22A1):​c.1277-97C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 879,112 control chromosomes in the GnomAD database, including 12,957 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 0.14 (1829 hom., cov: 32)
  • Exomes 𝑓: 0.17 (11128 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A1	NM_003057.3	c.1277-97C>G		intron_variant		ENST00000366963.9
SLC22A1	NM_153187.2	c.1277-97C>G		intron_variant
SLC22A1	XM_005267103.3	c.1277-97C>G		intron_variant
SLC22A1	XM_006715552.3	c.1277-97C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9	c.1277-97C>G		intron_variant		1	NM_003057.3	P1

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21215 AN: 152106 Hom.: 1820 Cov.: 32

Gnomad AFR AF: 0.0591

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.166 AC: 120510 AN: 726890 Hom.: 11128 AF XY: 0.167 AC XY: 63824 AN XY: 383160

Gnomad4 AFR exome AF: 0.0575

Gnomad4 AMR exome AF: 0.269

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.000364

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.145

Gnomad4 NFE exome AF: 0.179

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.140 AC: 21237 AN: 152222 Hom.: 1829 Cov.: 32 AF XY: 0.140 AC XY: 10426 AN XY: 74420

Gnomad4 AFR AF: 0.0591

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.161

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.142

Alfa AF: 0.160 Hom.: 1173

Bravo AF: 0.141

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.3
DANN	Benign	0.40

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: rs662138; hg19: chr6-160564476;