rs3939250

Positions:

• chr21-45545585-C-T
• chr21-45545585-C-A
• chr21-45545585-C-G

Variant summary

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

The NM_001352511.3(SLC19A1):​c.-49-7577G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.779 in 151,824 control chromosomes in the GnomAD database, including 46,878 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 0.78 (46878 hom., cov: 30)
• Consequence: SLC19A1 NM_001352511.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC19A1	NM_001352511.3	c.-49-7577G>A		intron_variant
SLC19A1	XM_011529696.3	c.-137-948G>A		intron_variant
SLC19A1	XM_011529700.3	c.-49-7577G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC19A1	ENST00000650808.1	c.-49-7577G>A		intron_variant				A2

Frequencies

GnomAD3 genomes AF: 0.779 AC: 118236 AN: 151706 Hom.: 46842 Cov.: 30

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.681

Gnomad EAS AF: 0.761

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.775

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.779 AC: 118320 AN: 151824 Hom.: 46878 Cov.: 30 AF XY: 0.780 AC XY: 57883 AN XY: 74184

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.718

Gnomad4 ASJ AF: 0.681

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.761

Alfa AF: 0.720 Hom.: 10902

Bravo AF: 0.781

Asia WGS AF: 0.778 AC: 2701 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3939250; hg19: chr21-46965499;