dbSNP rs2282142: SLC22A1:c.955-61G>A (chr6-160136483-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.955-61G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 1,543,926 control chromosomes in the GnomAD database, including 1,217 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 0.032 ( 139 hom., cov: 32)

Exomes 𝑓: 0.024 ( 1078 hom. )

Consequence

SLC22A1
NM_003057.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.329

Publications

7 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:

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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
SLC22A1	NM_003057.3 link	c.955-61G>A	intron_variant	Intron 5 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2 link	c.955-61G>A	intron_variant	Intron 5 of 9		NP_694857.1
SLC22A1	NM_001437335.1 link	c.955-61G>A	intron_variant	Intron 5 of 8		NP_001424264.1
SLC22A1	XM_005267103.3 link	c.955-61G>A	intron_variant	Intron 5 of 11		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9 link	c.955-61G>A		intron_variant	Intron 5 of 10	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes

AF:

0.0318

AC:

4839

AN:

152126

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0497

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0351

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.128

Gnomad SAS

AF:

0.0833

Gnomad FIN

AF:

0.00792

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.0229

GnomAD4 exome

AF:

0.0245

AC:

34078

AN:

1391682

Hom.:

1078

Cov.:

AF XY:

0.0260

AC XY:

18066

AN XY:

696128

show subpopulations

African (AFR)

AF:

0.0503

AC:

1606

AN:

31946

American (AMR)

AF:

0.0428

AC:

1908

AN:

44570

Ashkenazi Jewish (ASJ)

AF:

0.000312

AC:

AN:

25672

East Asian (EAS)

AF:

0.153

AC:

5985

AN:

39228

South Asian (SAS)

AF:

0.0728

AC:

6167

AN:

84756

European-Finnish (FIN)

AF:

0.00919

AC:

489

AN:

53236

Middle Eastern (MID)

AF:

0.0147

AC:

AN:

5632

European-Non Finnish (NFE)

AF:

0.0156

AC:

16374

AN:

1048630

Other (OTH)

AF:

0.0251

AC:

1458

AN:

58012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

1615

3230

4845

6460

8075

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

750

1500

2250

3000

3750

<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:

0.0318

AC:

4847

AN:

152244

Hom.:

139

Cov.:

AF XY:

0.0343

AC XY:

2554

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.0497

AC:

2064

AN:

41546

American (AMR)

AF:

0.0352

AC:

539

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3464

East Asian (EAS)

AF:

0.129

AC:

664

AN:

5152

South Asian (SAS)

AF:

0.0834

AC:

402

AN:

4820

European-Finnish (FIN)

AF:

0.00792

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0151

AC:

1026

AN:

68028

Other (OTH)

AF:

0.0227

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

220

440

660

880

1100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0234

Hom.:

110

Bravo

AF:

0.0332

Asia WGS

AF:

0.0900

AC:

313

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.84

(source)

DANN

Benign

0.66

PhyloP100

-0.33

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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