Genetic Variant SLC22A1:c.411+184G>A (chr6-160122530-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_003057.3(SLC22A1):c.411+184G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0895 in 893,046 control chromosomes in the GnomAD database, including 3,859 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 0.076 ( 505 hom., cov: 33)

Exomes 𝑓: 0.092 ( 3354 hom. )

Consequence

SLC22A1
NM_003057.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.658

Publications

23 publications found

Variant links:

Genes affected

SLC22A1 (HGNC:10963): (solute carrier family 22 member 1) 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. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [provided by RefSeq, Jul 2008]

SLC22A1 links:

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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=-0.83).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3 link	c.411+184G>A	intron_variant	Intron 1 of 10	ENST00000366963.9	NP_003048.1	O15245-1
SLC22A1	NM_153187.2 link	c.411+184G>A	intron_variant	Intron 1 of 9		NP_694857.1	O15245-2
SLC22A1	NM_001437335.1 link	c.411+184G>A	intron_variant	Intron 1 of 8		NP_001424264.1
SLC22A1	XM_005267103.3 link	c.411+184G>A	intron_variant	Intron 1 of 11		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9 link	c.411+184G>A		intron_variant	Intron 1 of 10	1	NM_003057.3	ENSP00000355930.4		O15245-1

Frequencies

GnomAD3 genomes

AF:

0.0763

AC:

11610

AN:

152140

Hom.:

505

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0406

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.0775

Gnomad ASJ

AF:

0.174

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.0850

Gnomad MID

AF:

0.0732

Gnomad NFE

AF:

0.0996

Gnomad OTH

AF:

0.0884

GnomAD4 exome

AF:

0.0922

AC:

68288

AN:

740788

Hom.:

3354

AF XY:

0.0928

AC XY:

31950

AN XY:

344222

show subpopulations

African (AFR)

AF:

0.0393

AC:

547

AN:

13902

American (AMR)

AF:

0.0557

AC:

AN:

898

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

744

AN:

4608

East Asian (EAS)

AF:

0.000939

AC:

AN:

3194

South Asian (SAS)

AF:

0.0249

AC:

366

AN:

14686

European-Finnish (FIN)

AF:

0.0932

AC:

AN:

236

Middle Eastern (MID)

AF:

0.117

AC:

171

AN:

1460

European-Non Finnish (NFE)

AF:

0.0948

AC:

64246

AN:

677676

Other (OTH)

AF:

0.0887

AC:

2139

AN:

24128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

2821

5642

8463

11284

14105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3210

6420

9630

12840

16050

<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:

0.0762

AC:

11607

AN:

152258

Hom.:

505

Cov.:

AF XY:

0.0740

AC XY:

5506

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.0405

AC:

1685

AN:

41558

American (AMR)

AF:

0.0774

AC:

1184

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

604

AN:

3470

East Asian (EAS)

AF:

0.000965

AC:

AN:

5182

South Asian (SAS)

AF:

0.0209

AC:

101

AN:

4826

European-Finnish (FIN)

AF:

0.0850

AC:

901

AN:

10600

Middle Eastern (MID)

AF:

0.0719

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0995

AC:

6769

AN:

68006

Other (OTH)

AF:

0.0875

AC:

185

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

551

1102

1652

2203

2754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

134

268

402

536

670

<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:

0.0904

Hom.:

2087

Bravo

AF:

0.0757

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

6.9

(source)

DANN

Benign

0.81

PhyloP100

0.66

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

Other links and lift over