rs443193

Positions:

• chr11-2915616-G-A

Variant summary

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

The NM_002555.6(SLC22A18):​c.537-1006G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 152,164 control chromosomes in the GnomAD database, including 15,195 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 0.44 (15195 hom., cov: 34)
• Consequence: SLC22A18 NM_002555.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

Genes affected

SLC22A18 (HGNC:10964): (solute carrier family 22 member 18) This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms' tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Several alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A18	NM_002555.6	c.537-1006G>A		intron_variant		ENST00000649076.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A18	ENST00000649076.2	c.537-1006G>A		intron_variant			NM_002555.6	P1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66883 AN: 152046 Hom.: 15188 Cov.: 34

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.389

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.438

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.440 AC: 66928 AN: 152164 Hom.: 15195 Cov.: 34 AF XY: 0.441 AC XY: 32789 AN XY: 74418

Gnomad4 AFR AF: 0.367

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.337

Gnomad4 SAS AF: 0.438

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.421

Alfa AF: 0.461 Hom.: 2796

Bravo AF: 0.422

Asia WGS AF: 0.380 AC: 1325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.51
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs443193; hg19: chr11-2936846;