Genetic Variant SLC19A1:c.-49-6456A>C (chr21-45544464-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001352511.3(SLC19A1):c.-49-6456A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC19A1
NM_001352511.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.316

Publications

26 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
SLC19A1	NM_001352511.3 link	c.-49-6456A>C	intron_variant	Intron 1 of 5	NP_001339440.1
SLC19A1	XM_011529696.3 link	c.32+5A>C	splice_region_variant, intron_variant	Intron 2 of 7	XP_011527998.1
SLC19A1	XM_047440954.1 link	c.32+5A>C	splice_region_variant, intron_variant	Intron 2 of 7	XP_047296910.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
SLC19A1	ENST00000650808.1 link	c.-49-6456A>C	intron_variant	Intron 1 of 5		ENSP00000498221.1
SLC19A1	ENST00000567670.5 link	c.-377A>C	upstream_gene_variant		1	ENSP00000457278.1
SLC19A1	ENST00000443742.1 link	c.-377A>C	upstream_gene_variant		3	ENSP00000411345.1
SLC19A1	ENST00000528477.1 link	c.-460A>C	upstream_gene_variant		4	ENSP00000435780.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

4988

Hom.:

AF XY:

0.00

AC XY:

AN XY:

2554

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

114

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

110

East Asian (EAS)

AF:

0.00

AC:

AN:

574

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

3186

Other (OTH)

AF:

0.00

AC:

AN:

248

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.1

(source)

DANN

Benign

0.68

PhyloP100

-0.32

PromoterAI

0.022

Neutral

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over