chr6-160130061-T-G

Variant names:

• chr6-160130061-T-G
• rs4646272
• NM_003057.3:c.412-43T>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003057.3(SLC22A1):​c.412-43T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 1,522,626 control chromosomes in the GnomAD database, including 13,784 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 0.10 (1465 hom., cov: 31)
  • Exomes 𝑓: 0.092 (12319 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.412-43T>G		intron_variant	Intron 1 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.412-43T>G		intron_variant	Intron 1 of 9		NP_694857.1
SLC22A1	XM_005267103.3	c.412-43T>G		intron_variant	Intron 1 of 11		XP_005267160.1
SLC22A1	XM_006715552.3	c.412-43T>G		intron_variant	Intron 1 of 8		XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.412-43T>G		intron_variant	Intron 1 of 10	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15399 AN: 152012 Hom.: 1464 Cov.: 31

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0551

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0934

GnomAD3 exomes AF: 0.147 AC: 36714 AN: 250566 Hom.: 5342 AF XY: 0.139 AC XY: 18775 AN XY: 135420

Gnomad AFR exome AF: 0.0871

Gnomad AMR exome AF: 0.316

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.525

Gnomad SAS exome AF: 0.175

Gnomad FIN exome AF: 0.0597

Gnomad NFE exome AF: 0.0646

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0919 AC: 125970 AN: 1370496 Hom.: 12319 Cov.: 21 AF XY: 0.0928 AC XY: 63815 AN XY: 687610

Gnomad4 AFR exome AF: 0.0868

Gnomad4 AMR exome AF: 0.300

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.545

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.0596

Gnomad4 NFE exome AF: 0.0630

Gnomad4 OTH exome AF: 0.0922

GnomAD4 genome AF: 0.101 AC: 15415 AN: 152130 Hom.: 1465 Cov.: 31 AF XY: 0.105 AC XY: 7843 AN XY: 74392

Gnomad4 AFR AF: 0.0870

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.514

Gnomad4 SAS AF: 0.179

Gnomad4 FIN AF: 0.0551

Gnomad4 NFE AF: 0.0670

Gnomad4 OTH AF: 0.0976

Alfa AF: 0.0741 Hom.: 914

Bravo AF: 0.113

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.031
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.27		Position offset: 43

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4646272; hg19: chr6-160551093; COSMIC: COSV61452924;