dbSNP rs662138: SLC22A1:c.1277-97C>G (chr6-160143444-C-G) – 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.1277-97C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 879,112 control chromosomes in the GnomAD database, including 12,957 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 0.14 ( 1829 hom., cov: 32)

Exomes 𝑓: 0.17 ( 11128 hom. )

Consequence

SLC22A1
NM_003057.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.127

Publications

33 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:

ENSG00000301636 (HGNC:):

ENSG00000301636 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=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3 link	c.1277-97C>G	intron_variant	Intron 7 of 10	ENST00000366963.9	NP_003048.1	O15245-1
SLC22A1	NM_153187.2 link	c.1277-97C>G	intron_variant	Intron 7 of 9		NP_694857.1	O15245-2
SLC22A1	NM_001437335.1 link	c.1277-97C>G	intron_variant	Intron 7 of 8		NP_001424264.1
SLC22A1	XM_005267103.3 link	c.1277-97C>G	intron_variant	Intron 7 of 11		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9 link	c.1277-97C>G		intron_variant	Intron 7 of 10	1	NM_003057.3	ENSP00000355930.4		O15245-1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21215

AN:

152106

Hom.:

1820

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0591

Gnomad AMI

AF:

0.0822

Gnomad AMR

AF:

0.221

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.160

Gnomad FIN

AF:

0.157

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.178

Gnomad OTH

AF:

0.143

GnomAD4 exome

AF:

0.166

AC:

120510

AN:

726890

Hom.:

11128

AF XY:

0.167

AC XY:

63824

AN XY:

383160

show subpopulations

African (AFR)

AF:

0.0575

AC:

1114

AN:

19370

American (AMR)

AF:

0.269

AC:

10363

AN:

38508

Ashkenazi Jewish (ASJ)

AF:

0.129

AC:

2522

AN:

19494

East Asian (EAS)

AF:

0.000364

AC:

AN:

35730

South Asian (SAS)

AF:

0.173

AC:

11313

AN:

65434

European-Finnish (FIN)

AF:

0.145

AC:

7379

AN:

50904

Middle Eastern (MID)

AF:

0.127

AC:

539

AN:

4258

European-Non Finnish (NFE)

AF:

0.179

AC:

81723

AN:

457120

Other (OTH)

AF:

0.154

AC:

5544

AN:

36072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

4918

9836

14754

19672

24590

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1506

3012

4518

6024

7530

<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:

0.140

AC:

21237

AN:

152222

Hom.:

1829

Cov.:

AF XY:

0.140

AC XY:

10426

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0591

AC:

2454

AN:

41538

American (AMR)

AF:

0.222

AC:

3393

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.122

AC:

422

AN:

3472

East Asian (EAS)

AF:

0.00231

AC:

AN:

5186

South Asian (SAS)

AF:

0.161

AC:

775

AN:

4826

European-Finnish (FIN)

AF:

0.157

AC:

1661

AN:

10600

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.178

AC:

12102

AN:

68006

Other (OTH)

AF:

0.142

AC:

299

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

920

1841

2761

3682

4602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

238

476

714

952

1190

<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:

0.160

Hom.:

1173

Bravo

AF:

0.141

Asia WGS

AF:

0.0690

AC:

240

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.3

(source)

DANN

Benign

0.40

PhyloP100

0.13

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