rs3827266

chr21-45555934-C-T

Variant summary

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

The ENST00000693093.2(ENSG00000288885):n.287C>T variant causes a non coding transcript exon 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: ENST00000693093.2 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

Genes affected

(HGNC:):

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=-0.75).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC19A1	NM_001352511.3	c.-50+6808G>A		intron_variant
SLC19A1	XM_011529696.3	c.-138+6808G>A		intron_variant
SLC19A1	XM_011529700.3	c.-50+6808G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000693093.2	n.287C>T		non_coding_transcript_exon_variant	1/1
SLC19A1	ENST00000650808.1	c.-50+6808G>A		intron_variant				A2

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

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.303

Gnomad4 OTH AF: 0.312

Alfa AF: 0.300 Hom.: 5806

Bravo AF: 0.344

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.5
Dann	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3827266; hg19: chr21-46975848;