rs16928809

Positions:

• chr11-2915722-G-A
• chr11-2915722-G-T

Variant summary

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

The NM_002555.6(SLC22A18):​c.537-900G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0753 in 152,282 control chromosomes in the GnomAD database, including 566 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 (566 hom., cov: 34)
• Consequence: SLC22A18 NM_002555.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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]

SLC22A18 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A18	NM_002555.6	c.537-900G>A		intron_variant		ENST00000649076.2	NP_002546.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A18	ENST00000649076.2	c.537-900G>A		intron_variant			NM_002555.6	ENSP00000497561.1

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 11464 AN: 152164 Hom.: 567 Cov.: 34

Gnomad AFR AF: 0.0189

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0818

Gnomad EAS AF: 0.0830

Gnomad SAS AF: 0.0941

Gnomad FIN AF: 0.0758

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0947

Gnomad OTH AF: 0.0800

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

GnomAD4 genome AF: 0.0753 AC: 11470 AN: 152282 Hom.: 566 Cov.: 34 AF XY: 0.0770 AC XY: 5732 AN XY: 74456

Gnomad4 AFR AF: 0.0188

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0818

Gnomad4 EAS AF: 0.0830

Gnomad4 SAS AF: 0.0948

Gnomad4 FIN AF: 0.0758

Gnomad4 NFE AF: 0.0947

Gnomad4 OTH AF: 0.0796

Alfa AF: 0.0894 Hom.: 1101

Bravo AF: 0.0777

Asia WGS AF: 0.0970 AC: 335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.95
DANN	Benign	0.38

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: rs16928809; hg19: chr11-2936952;