6-160154953-C-T

Variant names:

• chr6-160154953-C-T
• rs2297374
• NM_003057.3:c.1498+43C>T

Variant summary

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

The NM_003057.3(SLC22A1):​c.1498+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,419,170 control chromosomes in the GnomAD database, including 106,914 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 0.41 (13456 hom., cov: 31)
  • Exomes 𝑓: 0.38 (93458 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 45 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]

ENSG00000301636 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 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.1498+43C>T		intron	N/A	NP_003048.1	O15245-1
	SLC22A1	NM_153187.2		c.1386-1022C>T		intron	N/A	NP_694857.1	O15245-2
	SLC22A1	NM_001437335.1		c.1386-3563C>T		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.1498+43C>T		intron	N/A	ENSP00000355930.4	O15245-1
	SLC22A1	ENST00000898298.1		c.1612+43C>T		intron	N/A	ENSP00000568357.1
	SLC22A1	ENST00000898304.1		c.1585+43C>T		intron	N/A	ENSP00000568363.1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62700 AN: 151676 Hom.: 13448 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.428

GnomAD2 exomes AF: 0.371 AC: 86781 AN: 234008 AF XY: 0.375

Gnomad AFR exome AF: 0.527

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.504

Gnomad EAS exome AF: 0.327

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.383 AC: 485363 AN: 1267378 Hom.: 93458 Cov.: 17 AF XY: 0.383 AC XY: 244798 AN XY: 638454

African (AFR) AF: 0.532 AC: 15923 AN: 29918

American (AMR) AF: 0.246 AC: 10572 AN: 42902

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 12462 AN: 24550

East Asian (EAS) AF: 0.325 AC: 12571 AN: 38646

South Asian (SAS) AF: 0.369 AC: 29636 AN: 80270

European-Finnish (FIN) AF: 0.338 AC: 17829 AN: 52696

Middle Eastern (MID) AF: 0.515 AC: 2699 AN: 5240

European-Non Finnish (NFE) AF: 0.386 AC: 362204 AN: 939358

Other (OTH) AF: 0.399 AC: 21467 AN: 53798

GnomAD4 genome AF: 0.413 AC: 62745 AN: 151792 Hom.: 13456 Cov.: 31 AF XY: 0.408 AC XY: 30257 AN XY: 74198

African (AFR) AF: 0.522 AC: 21587 AN: 41344

American (AMR) AF: 0.302 AC: 4612 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 1797 AN: 3472

East Asian (EAS) AF: 0.329 AC: 1697 AN: 5154

South Asian (SAS) AF: 0.377 AC: 1811 AN: 4810

European-Finnish (FIN) AF: 0.336 AC: 3534 AN: 10528

Middle Eastern (MID) AF: 0.521 AC: 151 AN: 290

European-Non Finnish (NFE) AF: 0.384 AC: 26097 AN: 67916

Other (OTH) AF: 0.425 AC: 897 AN: 2110

Alfa AF: 0.395 Hom.: 21107

Bravo AF: 0.417

Asia WGS AF: 0.358 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.066
DANN	Benign	0.61
PhyloP100		-1.6
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: rs2297374; hg19: chr6-160575985; COSMIC: COSV61451517; COSMIC: COSV61451517;