dbSNP rs4646273: SLC22A1:c.515+97G>A (chr6-160130304-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.515+97G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 931,312 control chromosomes in the GnomAD database, including 5,512 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 0.054 ( 699 hom., cov: 31)

Exomes 𝑓: 0.067 ( 4813 hom. )

Consequence

SLC22A1
NM_003057.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.404

Publications

5 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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003057.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC22A1	NM_003057.3	MANE Select	c.515+97G>A	intron	N/A	NP_003048.1
SLC22A1	NM_153187.2		c.515+97G>A	intron	N/A	NP_694857.1
SLC22A1	NM_001437335.1		c.515+97G>A	intron	N/A	NP_001424264.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.515+97G>A	intron	N/A	ENSP00000355930.4
SLC22A1	ENST00000898298.1		c.629+97G>A	intron	N/A	ENSP00000568357.1
SLC22A1	ENST00000898304.1		c.515+97G>A	intron	N/A	ENSP00000568363.1

Frequencies

GnomAD3 genomes

AF:

0.0538

AC:

8181

AN:

152010

Hom.:

698

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0102

Gnomad AMI

AF:

0.0110

Gnomad AMR

AF:

0.144

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.379

Gnomad SAS

AF:

0.0858

Gnomad FIN

AF:

0.0423

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0382

Gnomad OTH

AF:

0.0547

GnomAD4 exome

AF:

0.0668

AC:

52040

AN:

779184

Hom.:

4813

AF XY:

0.0650

AC XY:

26710

AN XY:

410764

show subpopulations

African (AFR)

AF:

0.0102

AC:

196

AN:

19208

American (AMR)

AF:

0.246

AC:

8874

AN:

36144

Ashkenazi Jewish (ASJ)

AF:

0.00824

AC:

159

AN:

19290

East Asian (EAS)

AF:

0.389

AC:

14103

AN:

36232

South Asian (SAS)

AF:

0.0834

AC:

5573

AN:

66804

European-Finnish (FIN)

AF:

0.0449

AC:

1970

AN:

43840

Middle Eastern (MID)

AF:

0.0165

AC:

AN:

4252

European-Non Finnish (NFE)

AF:

0.0368

AC:

18970

AN:

516026

Other (OTH)

AF:

0.0568

AC:

2125

AN:

37388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

2018

4036

6053

8071

10089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

678

1356

2034

2712

3390

<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:

0.0538

AC:

8186

AN:

152128

Hom.:

699

Cov.:

AF XY:

0.0565

AC XY:

4205

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0101

AC:

421

AN:

41518

American (AMR)

AF:

0.144

AC:

2204

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.378

AC:

1944

AN:

5148

South Asian (SAS)

AF:

0.0861

AC:

415

AN:

4820

European-Finnish (FIN)

AF:

0.0423

AC:

448

AN:

10588

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0382

AC:

2597

AN:

67986

Other (OTH)

AF:

0.0594

AC:

125

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

337

675

1012

1350

1687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<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:

0.0422

Hom.:

470

Bravo

AF:

0.0640

Asia WGS

AF:

0.228

AC:

795

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.3

(source)

DANN

Benign

0.56

PhyloP100

0.40

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