dbSNP rs3788200: SLC19A1:c.189+1114T>C (chr21-45536657-A-G) – 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.189+1114T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.537 in 165,330 control chromosomes in the GnomAD database, including 24,154 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 0.54 ( 22279 hom., cov: 33)

Exomes 𝑓: 0.52 ( 1875 hom. )

Consequence

SLC19A1
NM_194255.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

21 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 Gene-Disease associations (from GenCC):

combined immunodeficiency
Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
immunodeficiency 114, folate-responsive
Inheritance: AR Classification: LIMITED Submitted by: ClinGen
megaloblastic anemia, folate-responsive
Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

SLC19A1 links:

Genome browser will be placed here

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=-0.95).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.589 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	UniProt
SLC19A1	NM_194255.4	MANE Select	c.189+1114T>C	intron	N/A	NP_919231.1	P41440-1
SLC19A1	NM_001352512.2		c.189+1114T>C	intron	N/A	NP_001339441.1	P41440-1
SLC19A1	NM_001205206.4		c.189+1114T>C	intron	N/A	NP_001192135.1	P41440-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC19A1	ENST00000311124.9	TSL:1 MANE Select	c.189+1114T>C	intron	N/A	ENSP00000308895.4	P41440-1
SLC19A1	ENST00000567670.5	TSL:1	c.189+1114T>C	intron	N/A	ENSP00000457278.1	H3BTQ3
SLC19A1	ENST00000380010.8	TSL:1	c.189+1114T>C	intron	N/A	ENSP00000369347.4	P41440-3

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81762

AN:

151938

Hom.:

22238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.455

Gnomad AMI

AF:

0.689

Gnomad AMR

AF:

0.577

Gnomad ASJ

AF:

0.606

Gnomad EAS

AF:

0.473

Gnomad SAS

AF:

0.606

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.573

Gnomad OTH

AF:

0.520

GnomAD4 exome

AF:

0.520

AC:

6899

AN:

13274

Hom.:

1875

AF XY:

0.522

AC XY:

3623

AN XY:

6944

show subpopulations

African (AFR)

AF:

0.360

AC:

103

AN:

286

American (AMR)

AF:

0.537

AC:

132

AN:

246

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

235

AN:

400

East Asian (EAS)

AF:

0.417

AC:

645

AN:

1548

South Asian (SAS)

AF:

0.527

AC:

AN:

110

European-Finnish (FIN)

AF:

0.519

AC:

853

AN:

1644

Middle Eastern (MID)

AF:

0.471

AC:

AN:

European-Non Finnish (NFE)

AF:

0.538

AC:

4458

AN:

8284

Other (OTH)

AF:

0.557

AC:

383

AN:

688

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

155

310

466

621

776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.538

AC:

81858

AN:

152056

Hom.:

22279

Cov.:

AF XY:

0.538

AC XY:

39998

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.456

AC:

18892

AN:

41448

American (AMR)

AF:

0.578

AC:

8852

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.606

AC:

2100

AN:

3468

East Asian (EAS)

AF:

0.472

AC:

2444

AN:

5176

South Asian (SAS)

AF:

0.607

AC:

2926

AN:

4820

European-Finnish (FIN)

AF:

0.549

AC:

5801

AN:

10560

Middle Eastern (MID)

AF:

0.524

AC:

154

AN:

294

European-Non Finnish (NFE)

AF:

0.573

AC:

38953

AN:

67968

Other (OTH)

AF:

0.526

AC:

1110

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

2011

4023

6034

8046

10057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.549

Hom.:

27730

Bravo

AF:

0.535

Asia WGS

AF:

0.551

AC:

1914

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.031

(source)

DANN

Benign

0.40

PhyloP100

-1.3

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