Genetic Variant NM_194255.4:c.1151+1035G>A (chr21-45529735-C-T) – 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.1151+1035G>A 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 149,526 control chromosomes in the GnomAD database, including 20,621 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 ( 20621 hom., cov: 31)

Consequence

SLC19A1
NM_194255.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0700

Publications

9 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:

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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=-0.86).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 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.1151+1035G>A	intron	N/A	NP_919231.1	P41440-1
SLC19A1	NM_001352512.2		c.1151+1035G>A	intron	N/A	NP_001339441.1	P41440-1
SLC19A1	NM_001205207.3		c.1031+1035G>A	intron	N/A	NP_001192136.1	P41440-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC19A1	ENST00000311124.9	TSL:1 MANE Select	c.1151+1035G>A	intron	N/A	ENSP00000308895.4	P41440-1
SLC19A1	ENST00000567670.5	TSL:1	c.1151+1035G>A	intron	N/A	ENSP00000457278.1	H3BTQ3
SLC19A1	ENST00000380010.8	TSL:1	c.1151+1035G>A	intron	N/A	ENSP00000369347.4	P41440-3

Frequencies

GnomAD3 genomes

AF:

0.518

AC:

77404

AN:

149406

Hom.:

20598

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.687

Gnomad AMR

AF:

0.570

Gnomad ASJ

AF:

0.620

Gnomad EAS

AF:

0.481

Gnomad SAS

AF:

0.609

Gnomad FIN

AF:

0.566

Gnomad MID

AF:

0.524

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.506

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.518

AC:

77462

AN:

149526

Hom.:

20621

Cov.:

AF XY:

0.519

AC XY:

37919

AN XY:

73086

show subpopulations

African (AFR)

AF:

0.359

AC:

14424

AN:

40182

American (AMR)

AF:

0.571

AC:

8641

AN:

15126

Ashkenazi Jewish (ASJ)

AF:

0.620

AC:

2140

AN:

3452

East Asian (EAS)

AF:

0.480

AC:

2399

AN:

4994

South Asian (SAS)

AF:

0.610

AC:

2890

AN:

4740

European-Finnish (FIN)

AF:

0.566

AC:

5803

AN:

10256

Middle Eastern (MID)

AF:

0.519

AC:

139

AN:

268

European-Non Finnish (NFE)

AF:

0.583

AC:

39338

AN:

67520

Other (OTH)

AF:

0.512

AC:

1066

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1875

3750

5626

7501

9376

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<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:

0.555

Hom.:

27600

Bravo

AF:

0.504

Asia WGS

AF:

0.529

AC:

1838

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.0

(source)

DANN

Benign

0.83

PhyloP100

0.070

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over