rs3827266

Variant names:

• chr21-45555934-C-T
• rs3827266
• ENST00000859469.1:c.-50+6808G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001352511.3(SLC19A1):​c.-50+6808G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,014 control chromosomes in the GnomAD database, including 9,276 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 0.35 (9276 hom., cov: 33)
• Consequence: SLC19A1 NM_001352511.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 9 publications found

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]

SLC19A1 Gene-Disease associations (from GenCC):

• combined immunodeficiency

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• immunodeficiency 114, folate-responsive

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• megaloblastic anemia, folate-responsive

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ENSG00000288885 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352511.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC19A1	NM_001352511.3		c.-50+6808G>A		intron	N/A	NP_001339440.1	P41440-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC19A1	ENST00000859469.1		c.-50+6808G>A		intron	N/A	ENSP00000529528.1
	SLC19A1	ENST00000859470.1		c.-50+6808G>A		intron	N/A	ENSP00000529529.1
	SLC19A1	ENST00000859471.1		c.-412+6808G>A		intron	N/A	ENSP00000529530.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52527 AN: 151896 Hom.: 9265 Cov.: 33

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.388

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.346 AC: 52571 AN: 152014 Hom.: 9276 Cov.: 33 AF XY: 0.350 AC XY: 26000 AN XY: 74294

African (AFR) AF: 0.404 AC: 16758 AN: 41472

American (AMR) AF: 0.335 AC: 5131 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 1000 AN: 3470

East Asian (EAS) AF: 0.454 AC: 2331 AN: 5140

South Asian (SAS) AF: 0.391 AC: 1884 AN: 4820

European-Finnish (FIN) AF: 0.361 AC: 3817 AN: 10574

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20569 AN: 67930

Other (OTH) AF: 0.312 AC: 658 AN: 2108

Alfa AF: 0.307 Hom.: 10160

Bravo AF: 0.344

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	5.5
DANN	Benign	0.88
PhyloP100		-1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3827266; hg19: chr21-46975848;