21-45516669-T-G

Variant names:

• chr21-45516669-T-G
• rs3788189
• NM_194255.4:c.1294-529A>C

Variant summary

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

The NM_194255.4(SLC19A1):​c.1294-529A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,058 control chromosomes in the GnomAD database, including 19,336 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 0.50 (19336 hom., cov: 33)
• Consequence: SLC19A1 NM_194255.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.16

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 (AFR) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC19A1	NM_194255.4	c.1294-529A>C		intron_variant	Intron 5 of 5	ENST00000311124.9	NP_919231.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC19A1	ENST00000311124.9	c.1294-529A>C		intron_variant	Intron 5 of 5	1	NM_194255.4	ENSP00000308895.4

Frequencies

GnomAD3 genomes AF: 0.496 AC: 75344 AN: 151940 Hom.: 19314 Cov.: 33

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.496 AC: 75403 AN: 152058 Hom.: 19336 Cov.: 33 AF XY: 0.496 AC XY: 36850 AN XY: 74322

Gnomad4 AFR AF: 0.635

Gnomad4 AMR AF: 0.446

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.557

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.504

Alfa AF: 0.328 Hom.: 857

Bravo AF: 0.502

Asia WGS AF: 0.529 AC: 1841 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	0.064
DANN	Benign	0.55

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: rs3788189; hg19: chr21-46936583; COSMIC: COSV60591987; COSMIC: COSV60591987;