rs3788205

Positions:

• chr21-45544464-T-C
• chr21-45544464-T-G

Variant summary

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

The XM_011529696.3(SLC19A1):​c.32+5A>G variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 157,112 control chromosomes in the GnomAD database, including 47,360 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 0.77 (46099 hom., cov: 33)
  • Exomes 𝑓: 0.70 (1261 hom.)
• Consequence: SLC19A1 XM_011529696.3 splice_donor_5th_base, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A1	NM_001352511.3	c.-49-6456A>G		intron_variant			NP_001339440.1
SLC19A1	XM_011529696.3	c.32+5A>G		splice_donor_5th_base_variant, intron_variant			XP_011527998.1
SLC19A1	XM_011529700.3	c.-49-6456A>G		intron_variant			XP_011528002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000650808.1	c.-49-6456A>G		intron_variant				ENSP00000498221	A2

Frequencies

GnomAD3 genomes AF: 0.772 AC: 117315 AN: 152042 Hom.: 46062 Cov.: 33

Gnomad AFR AF: 0.936

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.717

Gnomad ASJ AF: 0.658

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.737

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.759

GnomAD4 exome AF: 0.704 AC: 3486 AN: 4952 Hom.: 1261 AF XY: 0.712 AC XY: 1810 AN XY: 2542

Gnomad4 AFR exome AF: 0.894

Gnomad4 AMR exome AF: 0.711

Gnomad4 ASJ exome AF: 0.627

Gnomad4 EAS exome AF: 0.785

Gnomad4 SAS exome AF: 0.659

Gnomad4 FIN exome AF: 0.761

Gnomad4 NFE exome AF: 0.674

Gnomad4 OTH exome AF: 0.726

GnomAD4 genome AF: 0.772 AC: 117399 AN: 152160 Hom.: 46099 Cov.: 33 AF XY: 0.773 AC XY: 57492 AN XY: 74366

Gnomad4 AFR AF: 0.936

Gnomad4 AMR AF: 0.717

Gnomad4 ASJ AF: 0.658

Gnomad4 EAS AF: 0.769

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.769

Gnomad4 NFE AF: 0.695

Gnomad4 OTH AF: 0.752

Alfa AF: 0.711 Hom.: 53485

Bravo AF: 0.774

Asia WGS AF: 0.779 AC: 2707 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3788205; hg19: chr21-46964378;