11-2902596-A-G

Variant names:

• chr11-2902596-A-G
• rs367035
• ENST00000380574:c.-255A>G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PVS1_Supporting BP6_Very_Strong BA1

The NM_001315501.2(SLC22A18):​c.1A>G​(p.Met1?) variant causes a start lost 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 NM_001315501.2 start_lost
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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

Our verdict: Benign. The variant received -15 ACMG points.

• PVS1: Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 7 codons. Genomic position: 2902614. Lost 0.012 part of the original CDS.
• 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 rank	MANE	Protein	UniProt
SLC22A18	NM_002555.6	c.-133+232A>G		intron_variant	Intron 1 of 10	ENST00000649076.2	NP_002546.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A18	ENST00000649076.2	c.-133+232A>G		intron_variant	Intron 1 of 10		NM_002555.6	ENSP00000497561.1

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 AC: 3402 AN: 15786

Gnomad4 AMR exome AF: 0.490 AC: 482 AN: 984

Gnomad4 ASJ exome AF: 0.526 AC: 2712 AN: 5154

Gnomad4 EAS exome AF: 0.760 AC: 2761 AN: 3632

Gnomad4 SAS exome AF: 0.480 AC: 7898 AN: 16458

Gnomad4 FIN exome AF: 0.325 AC: 91 AN: 280

Gnomad4 NFE exome AF: 0.436 AC: 331793 AN: 761786

Gnomad4 Remaining exome AF: 0.458 AC: 12503 AN: 27292

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 AC: 0.223377 AN: 0.223377

Gnomad4 AMR AF: 0.498 AC: 0.498495 AN: 0.498495

Gnomad4 ASJ AF: 0.523 AC: 0.523041 AN: 0.523041

Gnomad4 EAS AF: 0.759 AC: 0.758929 AN: 0.758929

Gnomad4 SAS AF: 0.484 AC: 0.484018 AN: 0.484018

Gnomad4 FIN AF: 0.326 AC: 0.325847 AN: 0.325847

Gnomad4 NFE AF: 0.422 AC: 0.422425 AN: 0.422425

Gnomad4 OTH AF: 0.456 AC: 0.456439 AN: 0.456439

Alfa AF: 0.425 Hom.: 57262

Bravo AF: 0.396

Asia WGS AF: 0.555 AC: 1930 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jan 02, 2020

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.65
Mutation Taster		=300/0	polymorphism (auto)

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;