rs2297291

chr21-45525426-A-Gchr21-45525426-A-C

Variant summary

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

The NM_194255.4(SLC19A1):c.1293+391T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,170 control chromosomes in the GnomAD database, including 23,711 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 0.55 (23711 hom., cov: 35)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC19A1	NM_194255.4	c.1293+391T>C		intron_variant		ENST00000311124.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC19A1	ENST00000311124.9	c.1293+391T>C		intron_variant		1	NM_194255.4	A2

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84343 AN: 152052 Hom.: 23672 Cov.: 35

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.596

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.534

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

GnomAD4 genome AF: 0.555 AC: 84428 AN: 152170 Hom.: 23711 Cov.: 35 AF XY: 0.554 AC XY: 41187 AN XY: 74398

Gnomad4 AFR AF: 0.465

Gnomad4 AMR AF: 0.596

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.479

Gnomad4 SAS AF: 0.566

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.599

Gnomad4 OTH AF: 0.540

Alfa AF: 0.586 Hom.: 13623

Bravo AF: 0.552

Asia WGS AF: 0.544 AC: 1890 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.072
Dann	Benign	0.44
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2297291; hg19: chr21-46945340;