chr5-132340627-C-T

Variant names:

• chr5-132340627-C-T
• rs1050152
• NM_003059.3:c.1507C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003059.3(SLC22A4):​c.1507C>T​(p.Leu503Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,612,884 control chromosomes in the GnomAD database, including 122,654 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (7827 hom., cov: 31)
  • Exomes 𝑓: 0.38 (114827 hom.)
• Consequence: SLC22A4 NM_003059.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.226
• Publications: 198 publications found

Genes affected

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) 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. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

MIR3936HG (HGNC:40538): (MIR3936 host gene)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015764236).
• BP6: Variant 5-132340627-C-T is Benign according to our data. Variant chr5-132340627-C-T is described in ClinVar as Benign. ClinVar VariationId is 5750.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003059.3. 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
	SLC22A4	NM_003059.3	MANE Select	c.1507C>T	p.Leu503Phe	missense	Exon 9 of 10	NP_003050.2
	MIR3936HG	NR_110997.1		n.561-5701G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A4	ENST00000200652.4	TSL:1 MANE Select	c.1507C>T	p.Leu503Phe	missense	Exon 9 of 10	ENSP00000200652.3	Q9H015
	MIR3936HG	ENST00000621103.4	TSL:1	n.561-5701G>A		intron	N/A
	SLC22A4	ENST00000947750.1		c.1507C>T	p.Leu503Phe	missense	Exon 9 of 10	ENSP00000617809.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42572 AN: 151868 Hom.: 7830 Cov.: 31

Gnomad AFR AF: 0.0773

Gnomad AMI AF: 0.623

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.395

Gnomad EAS AF: 0.00251

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.326

GnomAD2 exomes AF: 0.294 AC: 73900 AN: 251468 AF XY: 0.297

Gnomad AFR exome AF: 0.0722

Gnomad AMR exome AF: 0.215

Gnomad ASJ exome AF: 0.415

Gnomad EAS exome AF: 0.00120

Gnomad FIN exome AF: 0.312

Gnomad NFE exome AF: 0.427

Gnomad OTH exome AF: 0.344

GnomAD4 exome AF: 0.378 AC: 551801 AN: 1460898 Hom.: 114827 Cov.: 34 AF XY: 0.372 AC XY: 270348 AN XY: 726798

African (AFR) AF: 0.0651 AC: 2178 AN: 33468

American (AMR) AF: 0.224 AC: 10028 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.416 AC: 10880 AN: 26124

East Asian (EAS) AF: 0.00106 AC: 42 AN: 39684

South Asian (SAS) AF: 0.127 AC: 10922 AN: 86236

European-Finnish (FIN) AF: 0.313 AC: 16692 AN: 53412

Middle Eastern (MID) AF: 0.228 AC: 1314 AN: 5768

European-Non Finnish (NFE) AF: 0.431 AC: 478486 AN: 1111124

Other (OTH) AF: 0.352 AC: 21259 AN: 60358

GnomAD4 genome AF: 0.280 AC: 42559 AN: 151986 Hom.: 7827 Cov.: 31 AF XY: 0.269 AC XY: 20004 AN XY: 74272

African (AFR) AF: 0.0771 AC: 3197 AN: 41484

American (AMR) AF: 0.297 AC: 4528 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.395 AC: 1372 AN: 3470

East Asian (EAS) AF: 0.00252 AC: 13 AN: 5166

South Asian (SAS) AF: 0.111 AC: 536 AN: 4826

European-Finnish (FIN) AF: 0.309 AC: 3252 AN: 10540

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28361 AN: 67932

Other (OTH) AF: 0.321 AC: 676 AN: 2104

Alfa AF: 0.372 Hom.: 50619

Bravo AF: 0.275

TwinsUK AF: 0.435 AC: 1612

ALSPAC AF: 0.437 AC: 1683

ESP6500AA AF: 0.0833 AC: 367

ESP6500EA AF: 0.419 AC: 3607

ExAC AF: 0.291 AC: 35363

Asia WGS AF: 0.0560 AC: 195 AN: 3478

EpiCase AF: 0.428

EpiControl AF: 0.434

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	SLC22A4 POLYMORPHISM (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	1.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.067	N
LIST_S2	Benign	0.85	D
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.23
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.15
Sift	Benign	0.10	T
Sift4G	Benign	0.12	T
Polyphen		0.0060	B
Vest4		0.036
MPC		0.30
ClinPred		0.0054	T
GERP RS		-4.6
Varity_R		0.14
gMVP		0.59
Mutation Taster		=94/6	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1050152; hg19: chr5-131676320; COSMIC: COSV52357336;