rs58188320

Variant names:

• chr21-45511090-T-TAC
• rs58188320
• NM_001379500.1:c.3694-16_3694-15dupAC

Your query was ambiguous. Multiple possible variants found:

• chr21-45511090-T-TAC
• chr21-45511090-T-TACAC
• chr21-45511090-T-TACACACACATAC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001379500.1(COL18A1):​c.3694-16_3694-15dupAC variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.64 (27743 hom., cov: 0)
  • Exomes 𝑓: 0.58 (175407 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.373
• Publications: 2 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 21-45511090-T-TAC is Benign according to our data. Variant chr21-45511090-T-TAC is described in ClinVar as [Benign]. Clinvar id is 261915.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL18A1	NM_001379500.1	c.3694-16_3694-15dupAC		intron_variant	Intron 40 of 41	ENST00000651438.1	NP_001366429.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL18A1	ENST00000651438.1	c.3694-21_3694-20insAC		intron_variant	Intron 40 of 41		NM_001379500.1	ENSP00000498485.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 84509 AN: 132052 Hom.: 27718 Cov.: 0

Gnomad AFR AF: 0.788

Gnomad AMI AF: 0.495

Gnomad AMR AF: 0.644

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.643

Gnomad NFE AF: 0.565

Gnomad OTH AF: 0.645

GnomAD2 exomes AF: 0.597 AC: 91110 AN: 152704 AF XY: 0.594

Gnomad AFR exome AF: 0.796

Gnomad AMR exome AF: 0.624

Gnomad ASJ exome AF: 0.535

Gnomad EAS exome AF: 0.623

Gnomad FIN exome AF: 0.624

Gnomad NFE exome AF: 0.550

Gnomad OTH exome AF: 0.611

GnomAD4 exome AF: 0.582 AC: 602616 AN: 1034716 Hom.: 175407 Cov.: 18 AF XY: 0.584 AC XY: 306063 AN XY: 523800

African (AFR) AF: 0.796 AC: 19634 AN: 24672

American (AMR) AF: 0.645 AC: 22413 AN: 34768

Ashkenazi Jewish (ASJ) AF: 0.576 AC: 12386 AN: 21488

East Asian (EAS) AF: 0.677 AC: 21553 AN: 31816

South Asian (SAS) AF: 0.610 AC: 44206 AN: 72488

European-Finnish (FIN) AF: 0.661 AC: 29247 AN: 44270

Middle Eastern (MID) AF: 0.665 AC: 3221 AN: 4846

European-Non Finnish (NFE) AF: 0.559 AC: 422594 AN: 755534

Other (OTH) AF: 0.610 AC: 27362 AN: 44834

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.640 AC: 84570 AN: 132146 Hom.: 27743 Cov.: 0 AF XY: 0.644 AC XY: 40683 AN XY: 63150

African (AFR) AF: 0.788 AC: 26875 AN: 34118

American (AMR) AF: 0.644 AC: 8394 AN: 13044

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1778 AN: 3276

East Asian (EAS) AF: 0.642 AC: 2693 AN: 4196

South Asian (SAS) AF: 0.632 AC: 2444 AN: 3866

European-Finnish (FIN) AF: 0.653 AC: 4965 AN: 7598

Middle Eastern (MID) AF: 0.660 AC: 173 AN: 262

European-Non Finnish (NFE) AF: 0.565 AC: 35658 AN: 63110

Other (OTH) AF: 0.639 AC: 1175 AN: 1838

Alfa AF: 0.342 Hom.: 750

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:1

Jun 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs58188320; hg19: chr21-46931004;