chr11-2903380-G-A

Position:

• chr11-2903380-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_002555.6(SLC22A18):​c.35G>A​(p.Arg12Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 1,612,552 control chromosomes in the GnomAD database, including 281,386 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.56 (24570 hom., cov: 32)
  • Exomes 𝑓: 0.59 (256816 hom.)
• Consequence: SLC22A18 NM_002555.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

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]

SLC22A18AS (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3087936E-6).
• BP6: Variant 11-2903380-G-A is Benign according to our data. Variant chr11-2903380-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A18	NM_002555.6	c.35G>A	p.Arg12Gln	missense_variant	2/11	ENST00000649076.2	NP_002546.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A18	ENST00000649076.2	c.35G>A	p.Arg12Gln	missense_variant	2/11		NM_002555.6	ENSP00000497561.1

Frequencies

GnomAD3 genomes AF: 0.563 AC: 85430 AN: 151834 Hom.: 24567 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.573

Gnomad OTH AF: 0.598

GnomAD3 exomes AF: 0.613 AC: 153048 AN: 249804 Hom.: 47589 AF XY: 0.614 AC XY: 83154 AN XY: 135510

Gnomad AFR exome AF: 0.476

Gnomad AMR exome AF: 0.642

Gnomad ASJ exome AF: 0.630

Gnomad EAS exome AF: 0.778

Gnomad SAS exome AF: 0.654

Gnomad FIN exome AF: 0.620

Gnomad NFE exome AF: 0.582

Gnomad OTH exome AF: 0.613

GnomAD4 exome AF: 0.591 AC: 863728 AN: 1460600 Hom.: 256816 Cov.: 55 AF XY: 0.593 AC XY: 431139 AN XY: 726598

Gnomad4 AFR exome AF: 0.482

Gnomad4 AMR exome AF: 0.633

Gnomad4 ASJ exome AF: 0.632

Gnomad4 EAS exome AF: 0.727

Gnomad4 SAS exome AF: 0.654

Gnomad4 FIN exome AF: 0.621

Gnomad4 NFE exome AF: 0.580

Gnomad4 OTH exome AF: 0.607

GnomAD4 genome AF: 0.562 AC: 85469 AN: 151952 Hom.: 24570 Cov.: 32 AF XY: 0.568 AC XY: 42176 AN XY: 74292

Gnomad4 AFR AF: 0.473

Gnomad4 AMR AF: 0.594

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.626

Gnomad4 NFE AF: 0.573

Gnomad4 OTH AF: 0.595

Alfa AF: 0.579 Hom.: 33934

Bravo AF: 0.562

TwinsUK AF: 0.562 AC: 2085

ALSPAC AF: 0.572 AC: 2206

ESP6500AA AF: 0.478 AC: 2107

ESP6500EA AF: 0.575 AC: 4948

ExAC AF: 0.607 AC: 73622

Asia WGS AF: 0.661 AC: 2297 AN: 3478

EpiCase AF: 0.589

EpiControl AF: 0.597

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	4.4
DANN	Benign	0.85
DEOGEN2	Benign	0.0017	T;T;T;.;T;.
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.38	.;.;.;T;T;T
MetaRNN	Benign	0.0000013	T;T;T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-1.6	N;N;N;.;N;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	0.93	N;N;.;N;N;N
REVEL	Benign	0.027
Sift	Benign	1.0	T;T;.;T;T;T
Sift4G	Benign	1.0	T;T;.;T;T;T
Polyphen		0.0010	B;B;B;B;B;.
Vest4		0.015
MPC		0.20
ClinPred		0.00014	T
GERP RS		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.015
gMVP		0.16

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: rs1048047; hg19: chr11-2924610; COSMIC: COSV56539474;