rs1888530

Positions:

• chr21-45516509-C-T
• chr21-45516509-C-G

Variant summary

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

The NM_194255.4(SLC19A1):​c.1294-369G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,120 control chromosomes in the GnomAD database, including 19,872 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 0.50 (19872 hom., cov: 34)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.02

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A1	NM_194255.4	c.1294-369G>A		intron_variant		ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9	c.1294-369G>A		intron_variant		1	NM_194255.4	ENSP00000308895.4

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76244 AN: 152000 Hom.: 19846 Cov.: 34

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.502 AC: 76304 AN: 152120 Hom.: 19872 Cov.: 34 AF XY: 0.502 AC XY: 37322 AN XY: 74362

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.448

Gnomad4 ASJ AF: 0.400

Gnomad4 EAS AF: 0.561

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.505

Alfa AF: 0.447 Hom.: 19346

Bravo AF: 0.508

Asia WGS AF: 0.537 AC: 1870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.40
DANN	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1888530; hg19: chr21-46936423; COSMIC: COSV60591985; COSMIC: COSV60591985;