Genetic Variant SLC22A4:c.1262-51G>A (chr5-132335767-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003059.3(SLC22A4):c.1262-51G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0196 in 1,439,874 control chromosomes in the GnomAD database, including 354 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.014 ( 27 hom., cov: 32)

Exomes 𝑓: 0.020 ( 327 hom. )

Consequence

SLC22A4
NM_003059.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.104

Publications

7 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0145 (2204/152314) while in subpopulation NFE AF = 0.0216 (1472/68024). AF 95% confidence interval is 0.0207. There are 27 homozygotes in GnomAd4. There are 1043 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003059.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A4	NM_003059.3	MANE Select	c.1262-51G>A		intron	N/A	NP_003050.2
	MIR3936HG	NR_110997.1		n.561-841C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC22A4	ENST00000200652.4	TSL:1 MANE Select	c.1262-51G>A	intron	N/A	ENSP00000200652.3	Q9H015
MIR3936HG	ENST00000621103.4	TSL:1	n.561-841C>T	intron	N/A
SLC22A4	ENST00000947750.1		c.1262-51G>A	intron	N/A	ENSP00000617809.1

Frequencies

GnomAD3 genomes

AF:

0.0145

AC:

2204

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00364

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0242

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0216

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.0171

AC:

4285

AN:

250286

AF XY:

0.0167

show subpopulations

Gnomad AFR exome

AF:

0.00334

Gnomad AMR exome

AF:

0.0258

Gnomad ASJ exome

AF:

0.00854

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0229

Gnomad NFE exome

AF:

0.0222

Gnomad OTH exome

AF:

0.0216

GnomAD4 exome

AF:

0.0202

AC:

25961

AN:

1287560

Hom.:

327

Cov.:

AF XY:

0.0195

AC XY:

12674

AN XY:

650212

show subpopulations

African (AFR)

AF:

0.00294

AC:

AN:

29972

American (AMR)

AF:

0.0254

AC:

1129

AN:

44476

Ashkenazi Jewish (ASJ)

AF:

0.00782

AC:

196

AN:

25074

East Asian (EAS)

AF:

0.0000515

AC:

AN:

38866

South Asian (SAS)

AF:

0.00358

AC:

295

AN:

82498

European-Finnish (FIN)

AF:

0.0230

AC:

1212

AN:

52798

Middle Eastern (MID)

AF:

0.00429

AC:

AN:

5132

European-Non Finnish (NFE)

AF:

0.0231

AC:

22049

AN:

954116

Other (OTH)

AF:

0.0177

AC:

968

AN:

54628

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1281

2563

3844

5126

6407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

784

1568

2352

3136

3920

<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:

0.0145

AC:

2204

AN:

152314

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1043

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.00366

AC:

152

AN:

41568

American (AMR)

AF:

0.0157

AC:

240

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00311

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0242

AC:

257

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0216

AC:

1472

AN:

68024

Other (OTH)

AF:

0.00992

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

114

229

343

458

572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.0189

Hom.:

Bravo

AF:

0.0142

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

-0.10

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over