chr11-2909210-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002555.6(SLC67A1):c.257G>A(p.Arg86His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00256 in 1,536,602 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0034 ( 17 hom., cov: 35)

Exomes 𝑓: 0.0025 ( 97 hom. )

Consequence

SLC67A1
NM_002555.6 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity no assertion criteria provided P:1B:1

Conservation

PhyloP100: -0.443

Publications

10 publications found

Variant links:

Genes affected

SLC67A1 (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]

SLC67A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030741394).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC67A1	NM_002555.6 link	c.257G>A	p.Arg86His	missense_variant	Exon 4 of 11	ENST00000649076.2	NP_002546.3	Q96BI1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A18	ENST00000649076.2 link	c.257G>A	p.Arg86His	missense_variant	Exon 4 of 11		NM_002555.6	ENSP00000497561.1		Q96BI1

Frequencies

GnomAD3 genomes

AF:

0.00342

AC:

521

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0560

Gnomad SAS

AF:

0.00662

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.0144

AC:

1958

AN:

135996

AF XY:

0.0120

show subpopulations

Gnomad AFR exome

AF:

0.000662

Gnomad AMR exome

AF:

0.0428

Gnomad ASJ exome

AF:

0.000642

Gnomad EAS exome

AF:

0.0699

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000750

Gnomad OTH exome

AF:

0.00772

GnomAD4 exome

AF:

0.00247

AC:

3417

AN:

1384292

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

1604

AN XY:

683808

show subpopulations

African (AFR)

AF:

0.000260

AC:

AN:

30820

American (AMR)

AF:

0.0345

AC:

1256

AN:

36406

Ashkenazi Jewish (ASJ)

AF:

0.000323

AC:

AN:

24768

East Asian (EAS)

AF:

0.0462

AC:

1669

AN:

36102

South Asian (SAS)

AF:

0.00205

AC:

161

AN:

78584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34756

Middle Eastern (MID)

AF:

0.000191

AC:

AN:

5246

European-Non Finnish (NFE)

AF:

0.0000454

AC:

AN:

1079902

Other (OTH)

AF:

0.00459

AC:

265

AN:

57708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

165

329

494

658

823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00343

AC:

522

AN:

152310

Hom.:

Cov.:

AF XY:

0.00395

AC XY:

294

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.000433

AC:

AN:

41572

American (AMR)

AF:

0.0110

AC:

169

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.0560

AC:

289

AN:

5162

South Asian (SAS)

AF:

0.00663

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68018

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

116

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00145

Hom.:

Bravo

AF:

0.00530

ExAC

AF:

0.00795

AC:

848

Asia WGS

AF:

0.0370

AC:

128

AN:

3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Rhabdomyosarcoma, somatic

Pathogenic:1

Mar 31, 1998

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

SLC22A18-related disorder

Benign:1

May 04, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.37

CADD

Benign

2.2

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.025

T;T;T;T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.087

LIST_S2

Benign

0.71

.;.;.;T;T

MetaRNN

Benign

0.0031

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.98

L;L;L;L;.

PhyloP100

-0.44

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.82

N;N;.;N;N

REVEL

Benign

0.028

Sift

Benign

0.52

T;T;.;T;T

Sift4G

Benign

0.56

T;T;.;T;T

Polyphen

0.11

B;B;B;B;.

Vest4

0.055

MPC

0.21

ClinPred

0.0040

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.036

gMVP

0.14

Mutation Taster

=87/13

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over