Variant chr5-139380072-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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

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:

SLC23A1 (HGNC:):

SLC23A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC23A1	NM_005847.5 linkuse as main transcript	c.652A>G	p.Ile218Val	missense_variant	7/15	ENST00000348729.8	NP_005838.3	Q9UHI7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC23A1	ENST00000348729.8 linkuse as main transcript	c.652A>G	p.Ile218Val	missense_variant	7/15	1	NM_005847.5	ENSP00000302701.4	Q9UHI7-1
SLC23A1	ENST00000353963.7 linkuse as main transcript	c.664A>G	p.Ile222Val	missense_variant	7/15	1		ENSP00000302851.5	Q9UHI7-2
SLC23A1	ENST00000504513.1 linkuse as main transcript	c.47A>G	p.His16Arg	missense_variant	2/4	5		ENSP00000422688.1	H0Y902
SLC23A1	ENST00000506512.1 linkuse as main transcript	n.142A>G		non_coding_transcript_exon_variant	1/2	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

GnomAD3 exomes

AF:

0.00151

AC:

364

AN:

241486

Hom.:

AF XY:

0.00110

AC XY:

143

AN XY:

130524

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 SAS exome

AF:

0.0000335

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

Gnomad4 AFR exome

AF:

0.0175

Gnomad4 AMR exome

AF:

0.00180

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.00593

AC:

901

AN:

151850

Hom.:

Cov.:

AF XY:

0.00579

AC XY:

430

AN XY:

74232

show subpopulations

Gnomad4 AFR

AF:

0.0201

Gnomad4 AMR

AF:

0.00341

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.00125

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

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

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over