Genetic Variant SLC22A1:c.412-207T>C (chr6-160129897-T-C) – 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.412-207T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 546,448 control chromosomes in the GnomAD database, including 33,407 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 0.37 ( 11166 hom., cov: 32)

Exomes 𝑓: 0.32 ( 22241 hom. )

Consequence

SLC22A1
NM_003057.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.91

Publications

6 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=-1.01).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3 link	c.412-207T>C	intron_variant	Intron 1 of 10	ENST00000366963.9	NP_003048.1	O15245-1
SLC22A1	NM_153187.2 link	c.412-207T>C	intron_variant	Intron 1 of 9		NP_694857.1	O15245-2
SLC22A1	NM_001437335.1 link	c.412-207T>C	intron_variant	Intron 1 of 8		NP_001424264.1
SLC22A1	XM_005267103.3 link	c.412-207T>C	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.412-207T>C		intron_variant	Intron 1 of 10	1	NM_003057.3	ENSP00000355930.4		O15245-1

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55576

AN:

151908

Hom.:

11131

Cov.:

show subpopulations

Gnomad AFR

AF:

0.518

Gnomad AMI

AF:

0.154

Gnomad AMR

AF:

0.390

Gnomad ASJ

AF:

0.229

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.353

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.283

Gnomad OTH

AF:

0.355

GnomAD4 exome

AF:

0.319

AC:

125681

AN:

394422

Hom.:

22241

Cov.:

AF XY:

0.319

AC XY:

66005

AN XY:

207210

show subpopulations

African (AFR)

AF:

0.519

AC:

5774

AN:

11116

American (AMR)

AF:

0.403

AC:

6599

AN:

16372

Ashkenazi Jewish (ASJ)

AF:

0.215

AC:

2610

AN:

12132

East Asian (EAS)

AF:

0.587

AC:

16126

AN:

27452

South Asian (SAS)

AF:

0.347

AC:

13385

AN:

38572

European-Finnish (FIN)

AF:

0.250

AC:

6669

AN:

26686

Middle Eastern (MID)

AF:

0.265

AC:

457

AN:

1726

European-Non Finnish (NFE)

AF:

0.281

AC:

66780

AN:

237574

Other (OTH)

AF:

0.319

AC:

7281

AN:

22792

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

3669

7338

11006

14675

18344

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

506

1012

1518

2024

2530

<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:

0.366

AC:

55663

AN:

152026

Hom.:

11166

Cov.:

AF XY:

0.365

AC XY:

27111

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.519

AC:

21517

AN:

41454

American (AMR)

AF:

0.389

AC:

5946

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

792

AN:

3464

East Asian (EAS)

AF:

0.550

AC:

2836

AN:

5154

South Asian (SAS)

AF:

0.353

AC:

1700

AN:

4816

European-Finnish (FIN)

AF:

0.249

AC:

2638

AN:

10588

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.283

AC:

19240

AN:

67956

Other (OTH)

AF:

0.358

AC:

758

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1739

3478

5217

6956

8695

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

532

1064

1596

2128

2660

<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:

0.328

Hom.:

3175

Bravo

AF:

0.386

Asia WGS

AF:

0.470

AC:

1636

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.49

(source)

DANN

Benign

0.27

PhyloP100

-1.9

PromoterAI

0.027

Neutral

(source)

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over