5-132301616-C-T

Position:

• chr5-132301616-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003059.3(SLC22A4):​c.393+6607C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0716 in 152,254 control chromosomes in the GnomAD database, including 532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.072 (532 hom., cov: 33)
• Consequence: SLC22A4 NM_003059.3 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: -1.40

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.393+6607C>T		intron_variant		ENST00000200652.4	NP_003050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.393+6607C>T		intron_variant		1	NM_003059.3	ENSP00000200652.3
SLC22A4	ENST00000491257.1	n.197+5995C>T		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10909 AN: 152136 Hom.: 535 Cov.: 33

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0458

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0767

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.0707

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0716 AC: 10908 AN: 152254 Hom.: 532 Cov.: 33 AF XY: 0.0710 AC XY: 5286 AN XY: 74448

Gnomad4 AFR AF: 0.0449

Gnomad4 AMR AF: 0.0457

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.0648

Gnomad4 FIN AF: 0.0767

Gnomad4 NFE AF: 0.0764

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.0734 Hom.: 441

Bravo AF: 0.0685

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Rheumatoid arthritis Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Dec 01, 2003

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.15
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs3792876; hg19: chr5-131637309;