Variant 11-2902596-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002555.6(SLC22A18):c.-133+232A>G variant causes a intron 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_002555.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.777

Variant links:

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 links:

SLC22A18AS (HGNC:10965): (SLC22A18 antisense RNA)

SLC22A18AS links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
SLC22A18	NM_002555.6 linkuse as main transcript	c.-133+232A>G		intron_variant		ENST00000649076.2	NP_002546.3
SLC22A18AS	NR_169305.1 linkuse as main transcript	n.231T>C		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A18	ENST00000649076.2 linkuse as main transcript	c.-133+232A>G		intron_variant			NM_002555.6	ENSP00000497561	P1
SLC22A18AS	ENST00000702349.1 linkuse as main transcript	n.355+863T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58622

AN:

151850

Hom.:

12621

Cov.:

show subpopulations

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.:

AF XY:

0.434

AC XY:

167042

AN XY:

384682

show subpopulations

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.:

AF XY:

0.386

AC XY:

28683

AN XY:

74276

show subpopulations

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:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

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

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over