rs13179900

Positions:

• chr5-132311897-G-A
• chr5-132311897-G-T

Variant summary

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

The NM_003059.3(SLC22A4):​c.394-264G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.083 in 553,826 control chromosomes in the GnomAD database, including 2,820 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 0.075 (548 hom., cov: 33)
  • Exomes 𝑓: 0.086 (2272 hom.)
• Consequence: SLC22A4 NM_003059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.256 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.394-264G>A		intron_variant		ENST00000200652.4	NP_003050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.394-264G>A		intron_variant		1	NM_003059.3	ENSP00000200652.3
MIR3936HG	ENST00000621103.4	n.1181C>T		non_coding_transcript_exon_variant	8/8	1
MIR3936HG	ENST00000669845.1	n.807C>T		non_coding_transcript_exon_variant	4/4
SLC22A4	ENST00000491257.1	n.198-264G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 11457 AN: 152110 Hom.: 551 Cov.: 33

Gnomad AFR AF: 0.0567

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0488

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.0650

Gnomad FIN AF: 0.0750

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0766

Gnomad OTH AF: 0.0747

GnomAD4 exome AF: 0.0859 AC: 34505 AN: 401598 Hom.: 2272 Cov.: 0 AF XY: 0.0845 AC XY: 17844 AN XY: 211234

Gnomad4 AFR exome AF: 0.0557

Gnomad4 AMR exome AF: 0.0388

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.0512

Gnomad4 FIN exome AF: 0.0735

Gnomad4 NFE exome AF: 0.0741

Gnomad4 OTH exome AF: 0.0827

GnomAD4 genome AF: 0.0753 AC: 11457 AN: 152228 Hom.: 548 Cov.: 33 AF XY: 0.0744 AC XY: 5534 AN XY: 74426

Gnomad4 AFR AF: 0.0567

Gnomad4 AMR AF: 0.0487

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.268

Gnomad4 SAS AF: 0.0649

Gnomad4 FIN AF: 0.0750

Gnomad4 NFE AF: 0.0766

Gnomad4 OTH AF: 0.0749

Alfa AF: 0.0701 Hom.: 522

Bravo AF: 0.0727

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.4
DANN	Benign	0.36

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: rs13179900; hg19: chr5-131647590; COSMIC: COSV52358926;