rs1131596

chr21-45538002-G-Achr21-45538002-G-Tchr21-45538002-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_194255.4(SLC19A1):c.-43C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,437,318 control chromosomes in the GnomAD database, including 221,635 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (20155 hom., cov: 32)
  • Exomes 𝑓: 0.56 (201480 hom.)
• Consequence: SLC19A1 NM_194255.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-45538002-G-A is Benign according to our data. Variant chr21-45538002-G-A is described in ClinVar as [Benign]. Clinvar id is 1220816.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC19A1	NM_194255.4	c.-43C>T		5_prime_UTR_variant	2/6	ENST00000311124.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC19A1	ENST00000311124.9	c.-43C>T		5_prime_UTR_variant	2/6	1	NM_194255.4	A2

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76469 AN: 151792 Hom.: 20135 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.593

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.571

Gnomad OTH AF: 0.494

GnomAD3 exomes AF: 0.522 AC: 47113 AN: 90294 Hom.: 12320 AF XY: 0.528 AC XY: 24752 AN XY: 46874

Gnomad AFR exome AF: 0.318

Gnomad AMR exome AF: 0.549

Gnomad ASJ exome AF: 0.577

Gnomad EAS exome AF: 0.442

Gnomad SAS exome AF: 0.568

Gnomad FIN exome AF: 0.524

Gnomad NFE exome AF: 0.548

Gnomad OTH exome AF: 0.523

GnomAD4 exome AF: 0.557 AC: 716515 AN: 1285408 Hom.: 201480 Cov.: 22 AF XY: 0.559 AC XY: 349314 AN XY: 625410

Gnomad4 AFR exome AF: 0.320

Gnomad4 AMR exome AF: 0.552

Gnomad4 ASJ exome AF: 0.588

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.546

Gnomad4 NFE exome AF: 0.567

Gnomad4 OTH exome AF: 0.545

GnomAD4 genome AF: 0.504 AC: 76519 AN: 151910 Hom.: 20155 Cov.: 32 AF XY: 0.505 AC XY: 37521 AN XY: 74230

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.548

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.500

Alfa AF: 0.559 Hom.: 12741

Bravo AF: 0.497

Asia WGS AF: 0.531 AC: 1844 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2019

This variant is associated with the following publications: (PMID: 17404734, 18053808) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1131596; hg19: chr21-46957916; COSMIC: COSV60756726; COSMIC: COSV60756726;