rs1051296

Positions:

• chr21-45514947-A-C

Variant summary

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

The ENST00000311124.9(SLC19A1):​c.*711T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 1,448,090 control chromosomes in the GnomAD database, including 141,948 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 0.45 (15206 hom., cov: 33)
  • Exomes 𝑓: 0.44 (126742 hom.)
• Consequence: SLC19A1 ENST00000311124.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.661

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 (EAS) allele frequency at 95% confidence interval = 0.541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A1	NM_194255.4	c.*711T>G		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.*711T>G		3_prime_UTR_variant	6/6	1	NM_194255.4	ENSP00000308895	A2

Frequencies

GnomAD3 genomes AF: 0.447 AC: 67820 AN: 151842 Hom.: 15197 Cov.: 33

Gnomad AFR AF: 0.465

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.481

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.471

GnomAD3 exomes AF: 0.432 AC: 34746 AN: 80472 Hom.: 7800 AF XY: 0.434 AC XY: 19559 AN XY: 45024

Gnomad AFR exome AF: 0.451

Gnomad AMR exome AF: 0.400

Gnomad ASJ exome AF: 0.387

Gnomad EAS exome AF: 0.544

Gnomad SAS exome AF: 0.460

Gnomad FIN exome AF: 0.430

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.441

GnomAD4 exome AF: 0.440 AC: 570280 AN: 1296128 Hom.: 126742 Cov.: 22 AF XY: 0.440 AC XY: 279957 AN XY: 635910

Gnomad4 AFR exome AF: 0.471

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.400

Gnomad4 EAS exome AF: 0.580

Gnomad4 SAS exome AF: 0.468

Gnomad4 FIN exome AF: 0.439

Gnomad4 NFE exome AF: 0.434

Gnomad4 OTH exome AF: 0.447

GnomAD4 genome AF: 0.446 AC: 67846 AN: 151962 Hom.: 15206 Cov.: 33 AF XY: 0.449 AC XY: 33380 AN XY: 74282

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.398

Gnomad4 EAS AF: 0.558

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.468

Alfa AF: 0.438 Hom.: 12888

Bravo AF: 0.446

Asia WGS AF: 0.508 AC: 1764 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	0.71
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1051296; hg19: chr21-46934861; COSMIC: COSV60589484; COSMIC: COSV60589484;