dbSNP rs34521685: SLC23A1:p.Ile218Val (chr5-139380072-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005847.5(SLC23A1):c.652A>G(p.Ile218Val) variant causes a missense change. The variant allele was found at a frequency of 0.00104 in 1,609,546 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0059 ( 5 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 4 hom. )

Consequence

SLC23A1
NM_005847.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.22

Publications

5 publications found

Variant links:

Genes affected

SLC23A1 (HGNC:10974): (solute carrier family 23 member 1) The absorption of vitamin C into the body and its distribution to organs requires two sodium-dependent vitamin C transporters. This gene encodes one of the two transporters. The encoded protein is active in bulk vitamin C transport involving epithelial surfaces. Previously, this gene had an official symbol of SLC23A2. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

SLC23A1 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 (MetaRNN=0.0082421005).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00593 (901/151850) while in subpopulation AFR AF = 0.0201 (832/41360). AF 95% confidence interval is 0.019. There are 5 homozygotes in GnomAd4. There are 430 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC23A1	NM_005847.5 link	c.652A>G	p.Ile218Val	missense_variant	Exon 7 of 15	ENST00000348729.8	NP_005838.3	Q9UHI7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC23A1	ENST00000348729.8 link	c.652A>G	p.Ile218Val	missense_variant	Exon 7 of 15	1	NM_005847.5	ENSP00000302701.4	Q9UHI7-1
SLC23A1	ENST00000353963.7 link	c.664A>G	p.Ile222Val	missense_variant	Exon 7 of 15	1		ENSP00000302851.5	Q9UHI7-2
SLC23A1	ENST00000504513.1 link	c.47A>G	p.His16Arg	missense_variant	Exon 2 of 4	5		ENSP00000422688.1	H0Y902
SLC23A1	ENST00000506512.1 link	n.142A>G		non_coding_transcript_exon_variant	Exon 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.00592

AC:

899

AN:

151732

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00341

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00623

GnomAD2 exomes

AF:

0.00151

AC:

364

AN:

241486

AF XY:

0.00110

show subpopulations

Gnomad AFR exome

AF:

0.0198

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000735

Gnomad OTH exome

AF:

0.00219

GnomAD4 exome

AF:

0.000535

AC:

780

AN:

1457696

Hom.:

Cov.:

AF XY:

0.000476

AC XY:

345

AN XY:

724706

show subpopulations

African (AFR)

AF:

0.0175

AC:

585

AN:

33430

American (AMR)

AF:

0.00180

AC:

AN:

43860

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26044

East Asian (EAS)

AF:

0.00

AC:

AN:

39596

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85712

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53182

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000225

AC:

AN:

1109900

Other (OTH)

AF:

0.00131

AC:

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

105

158

210

263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00593

AC:

901

AN:

151850

Hom.:

Cov.:

AF XY:

0.00579

AC XY:

430

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.0201

AC:

832

AN:

41360

American (AMR)

AF:

0.00341

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10574

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67918

Other (OTH)

AF:

0.00617

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00236

Hom.:

Bravo

AF:

0.00651

ESP6500AA

AF:

0.0193

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00170

AC:

206

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Benign

0.10

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.92

MetaRNN

Benign

0.0082

T;T

MetaSVM

Benign

-1.1

PhyloP100

6.2

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.39

N;N

REVEL

Benign

0.097

Sift

Benign

0.20

T;T

Sift4G

Benign

0.28

T;T

Vest4

0.41

MVP

0.48

MPC

0.77

ClinPred

0.061

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.39

Mutation Taster

=96/4

polymorphism

(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