21-45493600-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000417954.5(SLC19A1):c.*2735C>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 0.0156 in 1,525,146 control chromosomes in the GnomAD database, including 926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.034 ( 222 hom., cov: 34)

Exomes 𝑓: 0.014 ( 704 hom. )

Consequence

SLC19A1
ENST00000417954.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.422

Publications

2 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:

COL18A1 (HGNC:2195): (collagen type XVIII alpha 1 chain) This gene encodes the alpha chain of type XVIII collagen. This collagen is one of the multiplexins, extracellular matrix proteins that contain multiple triple-helix domains (collagenous domains) interrupted by non-collagenous domains. A long isoform of the protein has an N-terminal domain that is homologous to the extracellular part of frizzled receptors. Proteolytic processing at several endogenous cleavage sites in the C-terminal domain results in production of endostatin, a potent antiangiogenic protein that is able to inhibit angiogenesis and tumor growth. Mutations in this gene are associated with Knobloch syndrome. The main features of this syndrome involve retinal abnormalities, so type XVIII collagen may play an important role in retinal structure and in neural tube closure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]

COL18A1 Gene-Disease associations (from GenCC):

Knobloch syndrome 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
Knobloch syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Laboratory for Molecular Medicine
hereditary glaucoma, primary closed-angle
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

COL18A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 21-45493600-G-A is Benign according to our data. Variant chr21-45493600-G-A is described in ClinVar as Benign. ClinVar VariationId is 1286364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0892 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000417954.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COL18A1	NM_001379500.1	MANE Select	c.2352+25G>A	intron	N/A	NP_001366429.1	P39060-2
COL18A1	NM_130444.3		c.3597+25G>A	intron	N/A	NP_569711.2
COL18A1	NM_030582.4		c.2892+25G>A	intron	N/A	NP_085059.2	A0AAG2UXZ5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC19A1	ENST00000417954.5	TSL:1	c.*2735C>T	3_prime_UTR	Exon 5 of 5	ENSP00000393988.1	H0Y4T2
COL18A1	ENST00000651438.1	MANE Select	c.2352+25G>A	intron	N/A	ENSP00000498485.1	P39060-2
COL18A1	ENST00000355480.10	TSL:1	c.2892+25G>A	intron	N/A	ENSP00000347665.5	P39060-1

Frequencies

GnomAD3 genomes

AF:

0.0344

AC:

5234

AN:

152184

Hom.:

221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0915

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0167

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.0954

Gnomad SAS

AF:

0.0573

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00473

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.0221

AC:

3308

AN:

149486

AF XY:

0.0228

show subpopulations

Gnomad AFR exome

AF:

0.0958

Gnomad AMR exome

AF:

0.00651

Gnomad ASJ exome

AF:

0.00716

Gnomad EAS exome

AF:

0.0886

Gnomad FIN exome

AF:

0.00165

Gnomad NFE exome

AF:

0.00529

Gnomad OTH exome

AF:

0.0142

GnomAD4 exome

AF:

0.0135

AC:

18541

AN:

1372844

Hom.:

704

Cov.:

AF XY:

0.0140

AC XY:

9491

AN XY:

678590

show subpopulations

African (AFR)

AF:

0.101

AC:

3131

AN:

31114

American (AMR)

AF:

0.00759

AC:

271

AN:

35682

Ashkenazi Jewish (ASJ)

AF:

0.00804

AC:

201

AN:

25002

East Asian (EAS)

AF:

0.135

AC:

4805

AN:

35620

South Asian (SAS)

AF:

0.0448

AC:

3524

AN:

78674

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

47880

Middle Eastern (MID)

AF:

0.0111

AC:

AN:

4948

European-Non Finnish (NFE)

AF:

0.00509

AC:

5378

AN:

1056838

Other (OTH)

AF:

0.0195

AC:

1113

AN:

57086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

914

1829

2743

3658

4572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

344

688

1032

1376

1720

<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:

0.0344

AC:

5244

AN:

152302

Hom.:

222

Cov.:

AF XY:

0.0350

AC XY:

2603

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0916

AC:

3807

AN:

41564

American (AMR)

AF:

0.0167

AC:

255

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3470

East Asian (EAS)

AF:

0.0954

AC:

493

AN:

5168

South Asian (SAS)

AF:

0.0567

AC:

274

AN:

4832

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00473

AC:

322

AN:

68010

Other (OTH)

AF:

0.0255

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

247

494

741

988

1235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0172

Hom.:

Bravo

AF:

0.0374

Asia WGS

AF:

0.0680

AC:

237

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.31

(source)

DANN

Benign

0.77

PhyloP100

-0.42

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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