20-4869998-G-A

Variant names:

• chr20-4869998-G-A
• rs34460747
• NM_005116.6:c.1158C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_005116.6(SLC23A2):​c.1158C>T​(p.Ala386Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00226 in 1,613,662 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (31 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (43 hom.)
• Consequence: SLC23A2 NM_005116.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -8.79
• Publications: 0 publications found

Genes affected

SLC23A2 (HGNC:10973): (solute carrier family 23 member 2) 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 required transporters and the encoded protein accounts for tissue-specific uptake of vitamin C. Previously, this gene had an official symbol of SLC23A1. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.034).
• BP6: Variant 20-4869998-G-A is Benign according to our data. Variant chr20-4869998-G-A is described in ClinVar as Benign. ClinVar VariationId is 785650.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-8.8 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.012 (1830/152138) while in subpopulation AFR AF = 0.0413 (1713/41476). AF 95% confidence interval is 0.0397. There are 31 homozygotes in GnomAd4. There are 840 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1830 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005116.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC23A2	NM_005116.6	MANE Select	c.1158C>T	p.Ala386Ala	synonymous	Exon 12 of 17	NP_005107.4
	SLC23A2	NM_203327.2		c.1158C>T	p.Ala386Ala	synonymous	Exon 12 of 17	NP_976072.1	Q9UGH3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC23A2	ENST00000338244.6	TSL:1 MANE Select	c.1158C>T	p.Ala386Ala	synonymous	Exon 12 of 17	ENSP00000344322.1	Q9UGH3-1
	SLC23A2	ENST00000379333.5	TSL:1	c.1158C>T	p.Ala386Ala	synonymous	Exon 12 of 17	ENSP00000368637.1	Q9UGH3-1
	SLC23A2	ENST00000468355.5	TSL:1	n.1524C>T		non_coding_transcript_exon	Exon 12 of 12

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1822 AN: 152020 Hom.: 31 Cov.: 31

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00524

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00864

GnomAD2 exomes AF: 0.00342 AC: 858 AN: 250710 AF XY: 0.00241

Gnomad AFR exome AF: 0.0449

Gnomad AMR exome AF: 0.00287

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00124 AC: 1814 AN: 1461524 Hom.: 43 Cov.: 33 AF XY: 0.00105 AC XY: 767 AN XY: 727056

African (AFR) AF: 0.0413 AC: 1384 AN: 33472

American (AMR) AF: 0.00324 AC: 145 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000174 AC: 15 AN: 86242

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5742

European-Non Finnish (NFE) AF: 0.0000774 AC: 86 AN: 1111800

Other (OTH) AF: 0.00293 AC: 177 AN: 60376

GnomAD4 genome AF: 0.0120 AC: 1830 AN: 152138 Hom.: 31 Cov.: 31 AF XY: 0.0113 AC XY: 840 AN XY: 74396

African (AFR) AF: 0.0413 AC: 1713 AN: 41476

American (AMR) AF: 0.00530 AC: 81 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000250 AC: 17 AN: 67998

Other (OTH) AF: 0.00855 AC: 18 AN: 2106

Alfa AF: 0.00993 Hom.: 24

Bravo AF: 0.0137

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.012
DANN	Benign	0.87
PhyloP100		-8.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs34460747; hg19: chr20-4850644;