6-160129897-T-C

Variant names:

• chr6-160129897-T-C
• rs9457841
• NM_003057.3:c.412-207T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003057.3(SLC22A1):​c.412-207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 546,448 control chromosomes in the GnomAD database, including 33,407 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 0.37 (11166 hom., cov: 32)
  • Exomes 𝑓: 0.32 (22241 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003057.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	NM_003057.3	MANE Select	c.412-207T>C		intron	N/A	NP_003048.1	O15245-1
	SLC22A1	NM_153187.2		c.412-207T>C		intron	N/A	NP_694857.1	O15245-2
	SLC22A1	NM_001437335.1		c.412-207T>C		intron	N/A	NP_001424264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.412-207T>C		intron	N/A	ENSP00000355930.4	O15245-1
	SLC22A1	ENST00000540443.1	TSL:3	c.-372T>C		5_prime_UTR	Exon 1 of 3	ENSP00000440105.1	F5GY86
	SLC22A1	ENST00000898298.1		c.526-207T>C		intron	N/A	ENSP00000568357.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55576 AN: 151908 Hom.: 11131 Cov.: 32

Gnomad AFR AF: 0.518

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.319 AC: 125681 AN: 394422 Hom.: 22241 Cov.: 3 AF XY: 0.319 AC XY: 66005 AN XY: 207210

African (AFR) AF: 0.519 AC: 5774 AN: 11116

American (AMR) AF: 0.403 AC: 6599 AN: 16372

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 2610 AN: 12132

East Asian (EAS) AF: 0.587 AC: 16126 AN: 27452

South Asian (SAS) AF: 0.347 AC: 13385 AN: 38572

European-Finnish (FIN) AF: 0.250 AC: 6669 AN: 26686

Middle Eastern (MID) AF: 0.265 AC: 457 AN: 1726

European-Non Finnish (NFE) AF: 0.281 AC: 66780 AN: 237574

Other (OTH) AF: 0.319 AC: 7281 AN: 22792

GnomAD4 genome AF: 0.366 AC: 55663 AN: 152026 Hom.: 11166 Cov.: 32 AF XY: 0.365 AC XY: 27111 AN XY: 74336

African (AFR) AF: 0.519 AC: 21517 AN: 41454

American (AMR) AF: 0.389 AC: 5946 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 792 AN: 3464

East Asian (EAS) AF: 0.550 AC: 2836 AN: 5154

South Asian (SAS) AF: 0.353 AC: 1700 AN: 4816

European-Finnish (FIN) AF: 0.249 AC: 2638 AN: 10588

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19240 AN: 67956

Other (OTH) AF: 0.358 AC: 758 AN: 2116

Alfa AF: 0.328 Hom.: 3175

Bravo AF: 0.386

Asia WGS AF: 0.470 AC: 1636 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.49
DANN	Benign	0.27
PhyloP100		-1.9
PromoterAI		0.027	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9457841; hg19: chr6-160550929; COSMIC: COSV61452771;