chr21-45517713-C-T

Position:

• chr21-45517713-C-T

Variant summary

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

The NM_194255.4(SLC19A1):​c.1294-1573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 151,844 control chromosomes in the GnomAD database, including 16,347 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 (16347 hom., cov: 31)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.93

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.539 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC19A1	NM_194255.4	c.1294-1573G>A		intron_variant		ENST00000311124.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC19A1	ENST00000311124.9	c.1294-1573G>A		intron_variant		1	NM_194255.4	A2

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70047 AN: 151726 Hom.: 16333 Cov.: 31

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.485

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

GnomAD4 genome AF: 0.462 AC: 70086 AN: 151844 Hom.: 16347 Cov.: 31 AF XY: 0.464 AC XY: 34414 AN XY: 74194

Gnomad4 AFR AF: 0.512

Gnomad4 AMR AF: 0.436

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.481

Alfa AF: 0.445 Hom.: 12981

Bravo AF: 0.463

Asia WGS AF: 0.520 AC: 1807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.18
DANN	Benign	0.68

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: rs12482346; hg19: chr21-46937627;