rs3788199

Positions:

• chr21-45536504-A-G

Variant summary

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

The NM_194255.4(SLC19A1):​c.189+1267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,402 control chromosomes in the GnomAD database, including 21,002 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 0.52 (20953 hom., cov: 33)
  • Exomes 𝑓: 0.46 (49 hom.)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.576 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC19A1	NM_194255.4	c.189+1267T>C		intron_variant		ENST00000311124.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC19A1	ENST00000311124.9	c.189+1267T>C		intron_variant		1	NM_194255.4	A2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78682 AN: 151870 Hom.: 20922 Cov.: 33

Gnomad AFR AF: 0.391

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.602

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.503

GnomAD4 exome AF: 0.464 AC: 191 AN: 412 Hom.: 49 Cov.: 0 AF XY: 0.446 AC XY: 99 AN XY: 222

Gnomad4 AFR exome AF: 0.400

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.600

Gnomad4 EAS exome AF: 0.375

Gnomad4 SAS exome AF: 0.417

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.486

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.518 AC: 78754 AN: 151990 Hom.: 20953 Cov.: 33 AF XY: 0.519 AC XY: 38557 AN XY: 74286

Gnomad4 AFR AF: 0.391

Gnomad4 AMR AF: 0.569

Gnomad4 ASJ AF: 0.602

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.549

Gnomad4 NFE AF: 0.571

Gnomad4 OTH AF: 0.509

Alfa AF: 0.543 Hom.: 2881

Bravo AF: 0.513

Asia WGS AF: 0.535 AC: 1857 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.79

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: rs3788199; hg19: chr21-46956418; COSMIC: COSV60756707; COSMIC: COSV60756707;