11-2902596-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000380574.5(SLC22A18):c.-255A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 984,958 control chromosomes in the GnomAD database, including 92,179 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12613 hom., cov: 34)
  • Exomes 𝑓: 0.44 (79566 hom.)
• Consequence: SLC22A18 ENST00000380574.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.777

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:10965): (SLC22A18 antisense RNA)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 11-2902596-A-G is Benign according to our data. Variant chr11-2902596-A-G is described in ClinVar as [Benign]. Clinvar id is 768417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A18	NM_002555.6	c.-133+232A>G		intron_variant		ENST00000649076.2
SLC22A18AS	NR_169305.1	n.231T>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A18	ENST00000649076.2	c.-133+232A>G		intron_variant			NM_002555.6	P1
SLC22A18AS	ENST00000702349.1	n.355+863T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58622 AN: 151850 Hom.: 12621 Cov.: 34

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.485

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.459

GnomAD4 exome AF: 0.435 AC: 362495 AN: 832992 Hom.: 79566 Cov.: 33 AF XY: 0.434 AC XY: 167042 AN XY: 384682

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.490

Gnomad4 ASJ exome AF: 0.526

Gnomad4 EAS exome AF: 0.760

Gnomad4 SAS exome AF: 0.480

Gnomad4 FIN exome AF: 0.325

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.386 AC: 58625 AN: 151966 Hom.: 12613 Cov.: 34 AF XY: 0.386 AC XY: 28683 AN XY: 74276

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.498

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.759

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.456

Alfa AF: 0.432 Hom.: 23261

Bravo AF: 0.396

Asia WGS AF: 0.555 AC: 1930 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital

Jan 02, 2020

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	4.7
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs367035; hg19: chr11-2923826;