dbSNP rs3788199: SLC19A1:c.189+1267T>C (chr21-45536504-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+1267T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,402 control chromosomes in the GnomAD database, including 21,002 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 0.52 ( 20953 hom., cov: 33)

Exomes 𝑓: 0.46 ( 49 hom. )

Consequence

SLC19A1
NM_194255.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.670

Publications

4 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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.576 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+1267T>C	intron	N/A	NP_919231.1	P41440-1
SLC19A1	NM_001352512.2		c.189+1267T>C	intron	N/A	NP_001339441.1	P41440-1
SLC19A1	NM_001205206.4		c.189+1267T>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+1267T>C	intron	N/A	ENSP00000308895.4	P41440-1
SLC19A1	ENST00000567670.5	TSL:1	c.189+1267T>C	intron	N/A	ENSP00000457278.1	H3BTQ3
SLC19A1	ENST00000380010.8	TSL:1	c.189+1267T>C	intron	N/A	ENSP00000369347.4	P41440-3

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

78682

AN:

151870

Hom.:

20922

Cov.:

show subpopulations

Gnomad AFR

AF:

0.391

Gnomad AMI

AF:

0.688

Gnomad AMR

AF:

0.568

Gnomad ASJ

AF:

0.602

Gnomad EAS

AF:

0.472

Gnomad SAS

AF:

0.594

Gnomad FIN

AF:

0.549

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.572

Gnomad OTH

AF:

0.503

GnomAD4 exome

AF:

0.464

AC:

191

AN:

412

Hom.:

Cov.:

AF XY:

0.446

AC XY:

AN XY:

222

show subpopulations

African (AFR)

AF:

0.400

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.600

AC:

AN:

East Asian (EAS)

AF:

0.375

AC:

AN:

South Asian (SAS)

AF:

0.417

AC:

AN:

European-Finnish (FIN)

AF:

0.300

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.486

AC:

138

AN:

284

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

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:

0.518

AC:

78754

AN:

151990

Hom.:

20953

Cov.:

AF XY:

0.519

AC XY:

38557

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.391

AC:

16201

AN:

41448

American (AMR)

AF:

0.569

AC:

8699

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.602

AC:

2084

AN:

3464

East Asian (EAS)

AF:

0.471

AC:

2418

AN:

5130

South Asian (SAS)

AF:

0.594

AC:

2864

AN:

4818

European-Finnish (FIN)

AF:

0.549

AC:

5810

AN:

10574

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.571

AC:

38835

AN:

67954

Other (OTH)

AF:

0.509

AC:

1071

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1984

3968

5952

7936

9920

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<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:

0.537

Hom.:

2932

Bravo

AF:

0.513

Asia WGS

AF:

0.535

AC:

1857

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.2

(source)

DANN

Benign

0.79

PhyloP100

-0.67

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