Genetic Variant SLC22A4:c.498-85G>A (chr5-132313529-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003059.3(SLC22A4):c.498-85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0786 in 1,244,976 control chromosomes in the GnomAD database, including 5,114 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.073 ( 540 hom., cov: 33)

Exomes 𝑓: 0.079 ( 4574 hom. )

Consequence

SLC22A4
NM_003059.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.128

Publications

27 publications found

Variant links:

Genes affected

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

SLC22A4 links:

MIR3936HG (HGNC:40538): (MIR3936 host gene)

MIR3936HG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 5-132313529-G-A is Benign according to our data. Variant chr5-132313529-G-A is described in ClinVar as [Benign]. Clinvar id is 1280356.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A4	NM_003059.3 link	c.498-85G>A		intron_variant	Intron 2 of 9	ENST00000200652.4	NP_003050.2	Q9H015

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC22A4	ENST00000200652.4 link	c.498-85G>A	intron_variant	Intron 2 of 9	1	NM_003059.3	ENSP00000200652.3	Q9H015
MIR3936HG	ENST00000621103.4 link	n.825-1276C>T	intron_variant	Intron 7 of 7	1
SLC22A4	ENST00000491257.1 link	n.302-85G>A	intron_variant	Intron 2 of 3	4
MIR3936HG	ENST00000669845.1 link	n.451-1276C>T	intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0728

AC:

11080

AN:

152166

Hom.:

543

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0483

Gnomad AMI

AF:

0.109

Gnomad AMR

AF:

0.0479

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.0650

Gnomad FIN

AF:

0.0752

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0765

Gnomad OTH

AF:

0.0731

GnomAD4 exome

AF:

0.0794

AC:

86719

AN:

1092692

Hom.:

4574

AF XY:

0.0787

AC XY:

44149

AN XY:

560848

show subpopulations

African (AFR)

AF:

0.0453

AC:

1191

AN:

26276

American (AMR)

AF:

0.0330

AC:

1461

AN:

44286

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

2562

AN:

23784

East Asian (EAS)

AF:

0.293

AC:

11126

AN:

37968

South Asian (SAS)

AF:

0.0523

AC:

4108

AN:

78530

European-Finnish (FIN)

AF:

0.0758

AC:

4026

AN:

53110

Middle Eastern (MID)

AF:

0.0631

AC:

292

AN:

4624

European-Non Finnish (NFE)

AF:

0.0749

AC:

58096

AN:

775926

Other (OTH)

AF:

0.0800

AC:

3857

AN:

48188

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

4227

8454

12680

16907

21134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0728

AC:

11079

AN:

152284

Hom.:

540

Cov.:

AF XY:

0.0720

AC XY:

5362

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0483

AC:

2007

AN:

41562

American (AMR)

AF:

0.0478

AC:

732

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

364

AN:

3472

East Asian (EAS)

AF:

0.268

AC:

1388

AN:

5172

South Asian (SAS)

AF:

0.0648

AC:

313

AN:

4828

European-Finnish (FIN)

AF:

0.0752

AC:

798

AN:

10608

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0765

AC:

5204

AN:

68022

Other (OTH)

AF:

0.0733

AC:

155

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

521

1041

1562

2082

2603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0722

Hom.:

696

Bravo

AF:

0.0699

Asia WGS

AF:

0.122

AC:

426

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 16, 2021

GeneDx

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

-0.80

CADD

Benign

5.3

(source)

DANN

Benign

0.56

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(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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5-132313529-G-A

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