rs6886922

Positions:

• chr5-139382020-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The ENST00000348729.8(SLC23A1):​c.180C>T​(p.Ile60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 1,608,984 control chromosomes in the GnomAD database, including 607 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 0.034 (144 hom., cov: 31)
  • Exomes 𝑓: 0.019 (463 hom.)
• Consequence: SLC23A1 ENST00000348729.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.511

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=-0.511 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC23A1	NM_005847.5	c.180C>T	p.Ile60=	synonymous_variant	3/15	ENST00000348729.8	NP_005838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC23A1	ENST00000348729.8	c.180C>T	p.Ile60=	synonymous_variant	3/15	1	NM_005847.5	ENSP00000302701	P1

Frequencies

GnomAD3 genomes AF: 0.0343 AC: 5217 AN: 152134 Hom.: 143 Cov.: 31

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0317

Gnomad ASJ AF: 0.0865

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.00603

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.0335

GnomAD3 exomes AF: 0.0246 AC: 5915 AN: 240448 Hom.: 126 AF XY: 0.0235 AC XY: 3044 AN XY: 129744

Gnomad AFR exome AF: 0.0735

Gnomad AMR exome AF: 0.0278

Gnomad ASJ exome AF: 0.0871

Gnomad EAS exome AF: 0.0240

Gnomad SAS exome AF: 0.0176

Gnomad FIN exome AF: 0.00560

Gnomad NFE exome AF: 0.0162

Gnomad OTH exome AF: 0.0307

GnomAD4 exome AF: 0.0190 AC: 27743 AN: 1456732 Hom.: 463 Cov.: 32 AF XY: 0.0191 AC XY: 13815 AN XY: 724030

Gnomad4 AFR exome AF: 0.0697

Gnomad4 AMR exome AF: 0.0285

Gnomad4 ASJ exome AF: 0.0889

Gnomad4 EAS exome AF: 0.0289

Gnomad4 SAS exome AF: 0.0181

Gnomad4 FIN exome AF: 0.00558

Gnomad4 NFE exome AF: 0.0154

Gnomad4 OTH exome AF: 0.0261

GnomAD4 genome AF: 0.0343 AC: 5222 AN: 152252 Hom.: 144 Cov.: 31 AF XY: 0.0345 AC XY: 2568 AN XY: 74442

Gnomad4 AFR AF: 0.0715

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.0865

Gnomad4 EAS AF: 0.0259

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.00603

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.0364

Alfa AF: 0.0301 Hom.: 48

Bravo AF: 0.0382

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	7.5
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs6886922; hg19: chr5-138717709;