rs4819130

Variant names:

• chr21-45538385-C-T
• rs4819130
• NM_194255.4:c.-49-377G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_194255.4(SLC19A1):​c.-49-377G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,188 control chromosomes in the GnomAD database, including 20,197 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 0.50 (20197 hom., cov: 35)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.76

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC19A1	NM_194255.4	c.-49-377G>A		intron_variant	Intron 1 of 5	ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9	c.-49-377G>A		intron_variant	Intron 1 of 5	1	NM_194255.4	ENSP00000308895.4

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76621 AN: 152070 Hom.: 20177 Cov.: 35

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.468

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.504 AC: 76671 AN: 152188 Hom.: 20197 Cov.: 35 AF XY: 0.505 AC XY: 37605 AN XY: 74396

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.467

Gnomad4 SAS AF: 0.593

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.502

Alfa AF: 0.558 Hom.: 28107

Bravo AF: 0.496

Asia WGS AF: 0.529 AC: 1837 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.067
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4819130; hg19: chr21-46958299;