rs373823632

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001379500.1(COL18A1):c.3087+9_3087+10delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,510,956 control chromosomes in the GnomAD database, including 341 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 50 hom., cov: 34)

Exomes 𝑓: 0.016 ( 291 hom. )

Consequence

COL18A1
NM_001379500.1 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.246

Publications

0 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 -16 ACMG points.

BP6

Variant 21-45505438-GTC-G is Benign according to our data. Variant chr21-45505438-GTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 261907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0191 (2913/152308) while in subpopulation SAS AF = 0.0377 (182/4832). AF 95% confidence interval is 0.0332. There are 50 homozygotes in GnomAd4. There are 1542 alleles in the male GnomAd4 subpopulation. Median coverage is 34. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL18A1	NM_001379500.1 link	c.3087+9_3087+10delCT		intron_variant	Intron 36 of 41	ENST00000651438.1	NP_001366429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1 link	c.3087+8_3087+9delTC		splice_region_variant, intron_variant	Intron 36 of 41		NM_001379500.1	ENSP00000498485.1		P39060-2

Frequencies

GnomAD3 genomes

AF:

0.0190

AC:

2899

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.0176

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.0376

Gnomad FIN

AF:

0.0478

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0159

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.0206

AC:

4013

AN:

195062

AF XY:

0.0223

show subpopulations

Gnomad AFR exome

AF:

0.0195

Gnomad AMR exome

AF:

0.0110

Gnomad ASJ exome

AF:

0.0194

Gnomad EAS exome

AF:

0.00436

Gnomad FIN exome

AF:

0.0425

Gnomad NFE exome

AF:

0.0165

Gnomad OTH exome

AF:

0.0245

GnomAD4 exome

AF:

0.0163

AC:

22193

AN:

1358648

Hom.:

291

AF XY:

0.0172

AC XY:

11677

AN XY:

677534

show subpopulations

African (AFR)

AF:

0.0208

AC:

661

AN:

31818

American (AMR)

AF:

0.0106

AC:

407

AN:

38470

Ashkenazi Jewish (ASJ)

AF:

0.0169

AC:

424

AN:

25154

East Asian (EAS)

AF:

0.00171

AC:

AN:

38516

South Asian (SAS)

AF:

0.0359

AC:

2917

AN:

81352

European-Finnish (FIN)

AF:

0.0388

AC:

1890

AN:

48740

Middle Eastern (MID)

AF:

0.0443

AC:

181

AN:

4084

European-Non Finnish (NFE)

AF:

0.0141

AC:

14604

AN:

1033568

Other (OTH)

AF:

0.0183

AC:

1043

AN:

56946

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

994

1988

2983

3977

4971

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

528

1056

1584

2112

2640

<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:

0.0191

AC:

2913

AN:

152308

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1542

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0194

AC:

808

AN:

41566

American (AMR)

AF:

0.0121

AC:

185

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.0176

AC:

AN:

3472

East Asian (EAS)

AF:

0.00425

AC:

AN:

5182

South Asian (SAS)

AF:

0.0377

AC:

182

AN:

4832

European-Finnish (FIN)

AF:

0.0478

AC:

508

AN:

10626

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0159

AC:

1082

AN:

68002

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

144

288

433

577

721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<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:

0.0162

Hom.:

Bravo

AF:

0.0162

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

COL18A1: BS1, BS2; SLC19A1: BS1, BS2 -

not specified

Benign:2

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over