21-45528653-G-A

Position:

• chr21-45528653-G-A

Variant summary

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

The NM_194255.4(SLC19A1):​c.1151+2117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,056 control chromosomes in the GnomAD database, including 17,257 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 (17257 hom., cov: 33)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.235

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 (SAS) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC19A1	NM_194255.4	c.1151+2117C>T		intron_variant		ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9	c.1151+2117C>T		intron_variant		1	NM_194255.4	ENSP00000308895.4

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69243 AN: 151938 Hom.: 17239 Cov.: 33

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.606

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.456 AC: 69288 AN: 152056 Hom.: 17257 Cov.: 33 AF XY: 0.455 AC XY: 33815 AN XY: 74332

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.456

Gnomad4 ASJ AF: 0.626

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.453

Alfa AF: 0.506 Hom.: 6852

Bravo AF: 0.442

Asia WGS AF: 0.511 AC: 1775 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	1.1
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2838958; hg19: chr21-46948567;