NM_003057.3:c.955-61G>A

Variant names:

• chr6-160136483-G-A
• rs2282142
• NM_003057.3:c.955-61G>A

Variant summary

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

The NM_003057.3(SLC22A1):​c.955-61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 1,543,926 control chromosomes in the GnomAD database, including 1,217 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 0.032 (139 hom., cov: 32)
  • Exomes 𝑓: 0.024 (1078 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• Publications: 7 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	NM_003057.3	MANE Select	c.955-61G>A		intron	N/A	NP_003048.1
	SLC22A1	NM_153187.2		c.955-61G>A		intron	N/A	NP_694857.1
	SLC22A1	NM_001437335.1		c.955-61G>A		intron	N/A	NP_001424264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.955-61G>A		intron	N/A	ENSP00000355930.4
	SLC22A1	ENST00000324965.8	TSL:5	c.955-61G>A		intron	N/A	ENSP00000318103.4
	SLC22A1	ENST00000457470.6	TSL:5	c.955-61G>A		intron	N/A	ENSP00000409557.2

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4839 AN: 152126 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0351

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.0833

Gnomad FIN AF: 0.00792

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0229

GnomAD4 exome AF: 0.0245 AC: 34078 AN: 1391682 Hom.: 1078 Cov.: 24 AF XY: 0.0260 AC XY: 18066 AN XY: 696128

African (AFR) AF: 0.0503 AC: 1606 AN: 31946

American (AMR) AF: 0.0428 AC: 1908 AN: 44570

Ashkenazi Jewish (ASJ) AF: 0.000312 AC: 8 AN: 25672

East Asian (EAS) AF: 0.153 AC: 5985 AN: 39228

South Asian (SAS) AF: 0.0728 AC: 6167 AN: 84756

European-Finnish (FIN) AF: 0.00919 AC: 489 AN: 53236

Middle Eastern (MID) AF: 0.0147 AC: 83 AN: 5632

European-Non Finnish (NFE) AF: 0.0156 AC: 16374 AN: 1048630

Other (OTH) AF: 0.0251 AC: 1458 AN: 58012

GnomAD4 genome AF: 0.0318 AC: 4847 AN: 152244 Hom.: 139 Cov.: 32 AF XY: 0.0343 AC XY: 2554 AN XY: 74432

African (AFR) AF: 0.0497 AC: 2064 AN: 41546

American (AMR) AF: 0.0352 AC: 539 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3464

East Asian (EAS) AF: 0.129 AC: 664 AN: 5152

South Asian (SAS) AF: 0.0834 AC: 402 AN: 4820

European-Finnish (FIN) AF: 0.00792 AC: 84 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1026 AN: 68028

Other (OTH) AF: 0.0227 AC: 48 AN: 2116

Alfa AF: 0.0234 Hom.: 110

Bravo AF: 0.0332

Asia WGS AF: 0.0900 AC: 313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.84
DANN	Benign	0.66
PhyloP100		-0.33
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: rs2282142; hg19: chr6-160557515; COSMIC: COSV61452537; COSMIC: COSV61452537;