20-4977054-T-C

Variant names:

• chr20-4977054-T-C
• rs6053005
• NM_005116.6:c.-281-6135A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005116.6(SLC23A2):​c.-281-6135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,124 control chromosomes in the GnomAD database, including 35,368 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 0.66 (35368 hom., cov: 32)
• Consequence: SLC23A2 NM_005116.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.404
• Publications: 11 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC23A2	NM_005116.6	c.-281-6135A>G		intron_variant	Intron 1 of 16	ENST00000338244.6	NP_005107.4
SLC23A2	NM_203327.2	c.-281-6135A>G		intron_variant	Intron 1 of 16		NP_976072.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC23A2	ENST00000338244.6	c.-281-6135A>G		intron_variant	Intron 1 of 16	1	NM_005116.6	ENSP00000344322.1
SLC23A2	ENST00000379333.5	c.-281-6135A>G		intron_variant	Intron 1 of 16	1		ENSP00000368637.1
SLC23A2	ENST00000468355.5	n.90-6139A>G		intron_variant	Intron 1 of 11	1

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100910 AN: 152006 Hom.: 35305 Cov.: 32

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.639

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.664 AC: 101036 AN: 152124 Hom.: 35368 Cov.: 32 AF XY: 0.661 AC XY: 49141 AN XY: 74368

African (AFR) AF: 0.904 AC: 37531 AN: 41528

American (AMR) AF: 0.640 AC: 9771 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2143 AN: 3470

East Asian (EAS) AF: 0.454 AC: 2344 AN: 5166

South Asian (SAS) AF: 0.678 AC: 3270 AN: 4822

European-Finnish (FIN) AF: 0.532 AC: 5624 AN: 10572

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.563 AC: 38280 AN: 67976

Other (OTH) AF: 0.639 AC: 1346 AN: 2108

Alfa AF: 0.601 Hom.: 45122

Bravo AF: 0.680

Asia WGS AF: 0.596 AC: 2074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.3
DANN	Benign	0.43
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism (auto)

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: rs6053005; hg19: chr20-4957700;