rs1050351

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001379500.1(COL18A1):c.3447G>A(p.Ala1149Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.422 in 1,532,002 control chromosomes in the GnomAD database, including 138,426 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 14519 hom., cov: 32)

Exomes 𝑓: 0.42 ( 123907 hom. )

Consequence

COL18A1
NM_001379500.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -6.17

Publications

23 publications found

Variant links:

Genes affected

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 links:

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.005).

BP6

Variant 21-45509553-G-A is Benign according to our data. Variant chr21-45509553-G-A is described in ClinVar as Benign. ClinVar VariationId is 261910.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-6.17 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.542 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL18A1	NM_001379500.1 link	c.3447G>A	p.Ala1149Ala	synonymous_variant	Exon 39 of 42	ENST00000651438.1	NP_001366429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1 link	c.3447G>A	p.Ala1149Ala	synonymous_variant	Exon 39 of 42		NM_001379500.1	ENSP00000498485.1		P39060-2

Frequencies

GnomAD3 genomes

AF:

0.437

AC:

66217

AN:

151698

Hom.:

14513

Cov.:

show subpopulations

Gnomad AFR

AF:

0.458

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.484

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.559

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.432

Gnomad MID

AF:

0.491

Gnomad NFE

AF:

0.404

Gnomad OTH

AF:

0.450

GnomAD2 exomes

AF:

0.459

AC:

63247

AN:

137678

AF XY:

0.455

show subpopulations

Gnomad AFR exome

AF:

0.472

Gnomad AMR exome

AF:

0.535

Gnomad ASJ exome

AF:

0.379

Gnomad EAS exome

AF:

0.567

Gnomad FIN exome

AF:

0.437

Gnomad NFE exome

AF:

0.409

Gnomad OTH exome

AF:

0.463

GnomAD4 exome

AF:

0.421

AC:

580500

AN:

1380188

Hom.:

123907

Cov.:

AF XY:

0.421

AC XY:

287352

AN XY:

682112

show subpopulations

African (AFR)

AF:

0.467

AC:

14765

AN:

31624

American (AMR)

AF:

0.534

AC:

19517

AN:

36524

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

9672

AN:

25094

East Asian (EAS)

AF:

0.578

AC:

20817

AN:

36006

South Asian (SAS)

AF:

0.470

AC:

37358

AN:

79444

European-Finnish (FIN)

AF:

0.426

AC:

14701

AN:

34514

Middle Eastern (MID)

AF:

0.490

AC:

2597

AN:

5304

European-Non Finnish (NFE)

AF:

0.406

AC:

436307

AN:

1074006

Other (OTH)

AF:

0.429

AC:

24766

AN:

57672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

17558

35116

52673

70231

87789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13740

27480

41220

54960

68700

<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:

0.436

AC:

66247

AN:

151814

Hom.:

14519

Cov.:

AF XY:

0.441

AC XY:

32749

AN XY:

74180

show subpopulations

African (AFR)

AF:

0.457

AC:

18935

AN:

41398

American (AMR)

AF:

0.484

AC:

7391

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.384

AC:

1333

AN:

3470

East Asian (EAS)

AF:

0.559

AC:

2862

AN:

5118

South Asian (SAS)

AF:

0.478

AC:

2306

AN:

4822

European-Finnish (FIN)

AF:

0.432

AC:

4555

AN:

10544

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.404

AC:

27436

AN:

67874

Other (OTH)

AF:

0.446

AC:

942

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1922

3844

5766

7688

9610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.416

Hom.:

4315

Bravo

AF:

0.442

Asia WGS

AF:

0.509

AC:

1770

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Knobloch syndrome

Benign:4

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 23, 2017

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 28, 2017

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Oct 09, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary glaucoma, primary closed-angle

Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.38

(source)

DANN

Benign

0.63

PhyloP100

-6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

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

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over