Genetic Variant SLC19A1:c.*746C>T (chr21-45514912-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_194255.4(SLC19A1):c.*746C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 1,285,862 control chromosomes in the GnomAD database, including 130,437 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 0.46 ( 16600 hom., cov: 33)

Exomes 𝑓: 0.45 ( 113837 hom. )

Consequence

SLC19A1
NM_194255.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71

Publications

37 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=-0.98).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194255.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC19A1	NM_194255.4	MANE Select	c.*746C>T	3_prime_UTR	Exon 6 of 6	NP_919231.1
SLC19A1	NM_001352512.2		c.*746C>T	3_prime_UTR	Exon 6 of 6	NP_001339441.1
SLC19A1	NM_001205207.3		c.*746C>T	3_prime_UTR	Exon 5 of 5	NP_001192136.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC19A1	ENST00000311124.9	TSL:1 MANE Select	c.*746C>T	3_prime_UTR	Exon 6 of 6	ENSP00000308895.4
SLC19A1	ENST00000380010.8	TSL:1	c.*64C>T	3_prime_UTR	Exon 6 of 6	ENSP00000369347.4
SLC19A1	ENST00000567670.5	TSL:1	c.1293+10905C>T	intron	N/A	ENSP00000457278.1

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70592

AN:

151890

Hom.:

16589

Cov.:

show subpopulations

Gnomad AFR

AF:

0.522

Gnomad AMI

AF:

0.408

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.552

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.446

Gnomad MID

AF:

0.497

Gnomad NFE

AF:

0.432

Gnomad OTH

AF:

0.485

GnomAD4 exome

AF:

0.446

AC:

506192

AN:

1133850

Hom.:

113837

Cov.:

AF XY:

0.447

AC XY:

248916

AN XY:

556756

show subpopulations

African (AFR)

AF:

0.535

AC:

12263

AN:

22932

American (AMR)

AF:

0.431

AC:

6318

AN:

14666

Ashkenazi Jewish (ASJ)

AF:

0.401

AC:

7270

AN:

18112

East Asian (EAS)

AF:

0.577

AC:

17164

AN:

29754

South Asian (SAS)

AF:

0.506

AC:

28154

AN:

55620

European-Finnish (FIN)

AF:

0.438

AC:

19390

AN:

44228

Middle Eastern (MID)

AF:

0.521

AC:

2172

AN:

4168

European-Non Finnish (NFE)

AF:

0.437

AC:

391661

AN:

896632

Other (OTH)

AF:

0.457

AC:

21800

AN:

47738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

13541

27083

40624

54166

67707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11944

23888

35832

47776

59720

<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:

0.465

AC:

70628

AN:

152012

Hom.:

16600

Cov.:

AF XY:

0.467

AC XY:

34717

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.522

AC:

21648

AN:

41468

American (AMR)

AF:

0.436

AC:

6673

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

1381

AN:

3468

East Asian (EAS)

AF:

0.553

AC:

2830

AN:

5120

South Asian (SAS)

AF:

0.522

AC:

2518

AN:

4822

European-Finnish (FIN)

AF:

0.446

AC:

4709

AN:

10570

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.432

AC:

29335

AN:

67958

Other (OTH)

AF:

0.482

AC:

1016

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1981

3962

5944

7925

9906

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.445

Hom.:

15976

Bravo

AF:

0.466

Asia WGS

AF:

0.532

AC:

1850

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.55

(source)

DANN

Benign

0.55

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over