dbSNP rs3788205: SLC19A1:c.-49-6456A>G (chr21-45544464-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001352511.3(SLC19A1):c.-49-6456A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 157,112 control chromosomes in the GnomAD database, including 47,360 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 0.77 ( 46099 hom., cov: 33)

Exomes 𝑓: 0.70 ( 1261 hom. )

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
SLC19A1	ENST00000650808.1 link	c.-49-6456A>G	intron_variant	Intron 1 of 5		ENSP00000498221.1	P41440-3
SLC19A1	ENST00000567670.5 link	c.-377A>G	upstream_gene_variant		1	ENSP00000457278.1	H3BTQ3
SLC19A1	ENST00000443742.1 link	c.-377A>G	upstream_gene_variant		3	ENSP00000411345.1	C9J8K6
SLC19A1	ENST00000528477.1 link	c.-460A>G	upstream_gene_variant		4	ENSP00000435780.1	E9PIL5

Frequencies

GnomAD3 genomes

AF:

0.772

AC:

117315

AN:

152042

Hom.:

46062

Cov.:

show subpopulations

Gnomad AFR

AF:

0.936

Gnomad AMI

AF:

0.629

Gnomad AMR

AF:

0.717

Gnomad ASJ

AF:

0.658

Gnomad EAS

AF:

0.768

Gnomad SAS

AF:

0.737

Gnomad FIN

AF:

0.769

Gnomad MID

AF:

0.772

Gnomad NFE

AF:

0.695

Gnomad OTH

AF:

0.759

GnomAD4 exome

AF:

0.704

AC:

3486

AN:

4952

Hom.:

1261

AF XY:

0.712

AC XY:

1810

AN XY:

2542

show subpopulations

African (AFR)

AF:

0.894

AC:

AN:

American (AMR)

AF:

0.711

AC:

AN:

114

Ashkenazi Jewish (ASJ)

AF:

0.627

AC:

AN:

110

East Asian (EAS)

AF:

0.785

AC:

449

AN:

572

South Asian (SAS)

AF:

0.659

AC:

AN:

European-Finnish (FIN)

AF:

0.761

AC:

452

AN:

594

Middle Eastern (MID)

AF:

0.700

AC:

AN:

European-Non Finnish (NFE)

AF:

0.674

AC:

2128

AN:

3156

Other (OTH)

AF:

0.726

AC:

180

AN:

248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

142

190

237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.772

AC:

117399

AN:

152160

Hom.:

46099

Cov.:

AF XY:

0.773

AC XY:

57492

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.936

AC:

38875

AN:

41534

American (AMR)

AF:

0.717

AC:

10952

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.658

AC:

2283

AN:

3470

East Asian (EAS)

AF:

0.769

AC:

3968

AN:

5162

South Asian (SAS)

AF:

0.735

AC:

3549

AN:

4830

European-Finnish (FIN)

AF:

0.769

AC:

8142

AN:

10590

Middle Eastern (MID)

AF:

0.762

AC:

224

AN:

294

European-Non Finnish (NFE)

AF:

0.695

AC:

47244

AN:

67974

Other (OTH)

AF:

0.752

AC:

1590

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1338

2676

4013

5351

6689

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

850

1700

2550

3400

4250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.723

Hom.:

122580

Bravo

AF:

0.774

Asia WGS

AF:

0.779

AC:

2707

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.3

(source)

DANN

Benign

0.68

PhyloP100

-0.32

PromoterAI

0.038

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over