rs12482346

Variant names:

• chr21-45517713-C-T
• rs12482346
• NM_194255.4:c.1294-1573G>A

Variant summary

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

The NM_194255.4(SLC19A1):​c.1294-1573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,844 control chromosomes in the GnomAD database, including 16,347 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 0.46 (16347 hom., cov: 31)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93
• Publications: 11 publications found

Genes affected

SLC19A1 (HGNC:10937): (solute carrier family 19 member 1) The membrane protein encoded by this gene is a transporter of folate and is involved in the regulation of intracellular concentrations of folate. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194255.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC19A1	NM_194255.4	MANE Select	c.1294-1573G>A		intron	N/A	NP_919231.1
	SLC19A1	NM_001352512.2		c.1294-1573G>A		intron	N/A	NP_001339441.1
	SLC19A1	NM_001205207.3		c.1174-1573G>A		intron	N/A	NP_001192136.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC19A1	ENST00000311124.9	TSL:1 MANE Select	c.1294-1573G>A		intron	N/A	ENSP00000308895.4
	SLC19A1	ENST00000567670.5	TSL:1	c.1293+8104G>A		intron	N/A	ENSP00000457278.1
	SLC19A1	ENST00000380010.8	TSL:1	c.1294-2561G>A		intron	N/A	ENSP00000369347.4

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70047 AN: 151726 Hom.: 16333 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.462 AC: 70086 AN: 151844 Hom.: 16347 Cov.: 31 AF XY: 0.464 AC XY: 34414 AN XY: 74194

African (AFR) AF: 0.512 AC: 21201 AN: 41390

American (AMR) AF: 0.436 AC: 6665 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1364 AN: 3472

East Asian (EAS) AF: 0.556 AC: 2860 AN: 5140

South Asian (SAS) AF: 0.496 AC: 2392 AN: 4818

European-Finnish (FIN) AF: 0.444 AC: 4679 AN: 10532

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.433 AC: 29398 AN: 67906

Other (OTH) AF: 0.481 AC: 1012 AN: 2104

Alfa AF: 0.449 Hom.: 17289

Bravo AF: 0.463

Asia WGS AF: 0.520 AC: 1807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.68
PhyloP100		-1.9
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: rs12482346; hg19: chr21-46937627;