rs1051298

Positions:

• chr21-45514912-G-A

Variant summary

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

The NM_194255.4(SLC19A1):​c.*746C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,285,862 control chromosomes in the GnomAD database, including 130,437 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 (16600 hom., cov: 33)
  • Exomes 𝑓: 0.45 (113837 hom.)
• Consequence: SLC19A1 NM_194255.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A1	NM_194255.4	c.*746C>T		3_prime_UTR_variant	6/6	ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9	c.*746C>T		3_prime_UTR_variant	6/6	1	NM_194255.4	ENSP00000308895	A2

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70592 AN: 151890 Hom.: 16589 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.552

Gnomad SAS AF: 0.522

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.446 AC: 506192 AN: 1133850 Hom.: 113837 Cov.: 16 AF XY: 0.447 AC XY: 248916 AN XY: 556756

Gnomad4 AFR exome AF: 0.535

Gnomad4 AMR exome AF: 0.431

Gnomad4 ASJ exome AF: 0.401

Gnomad4 EAS exome AF: 0.577

Gnomad4 SAS exome AF: 0.506

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.437

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome AF: 0.465 AC: 70628 AN: 152012 Hom.: 16600 Cov.: 33 AF XY: 0.467 AC XY: 34717 AN XY: 74284

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.553

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.482

Alfa AF: 0.435 Hom.: 9578

Bravo AF: 0.466

Asia WGS AF: 0.532 AC: 1850 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.55
DANN	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Publications

LitVar

Other links and lift over

dbSNP: rs1051298; hg19: chr21-46934826; COSMIC: COSV60589480; COSMIC: COSV60589480;