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. Variant got -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

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

Verdict is Benign. Variant got -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

GnomAD3 exomes AF: 0.597 AC: 91110 AN: 152704 Hom.: 27709 AF XY: 0.594 AC XY: 48315 AN XY: 81366

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 SAS exome AF: 0.608

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

Gnomad4 AFR exome AF: 0.796

Gnomad4 AMR exome AF: 0.645

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.677

Gnomad4 SAS exome AF: 0.610

Gnomad4 FIN exome AF: 0.661

Gnomad4 NFE exome AF: 0.559

Gnomad4 OTH exome AF: 0.610

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

Gnomad4 AFR AF: 0.788

Gnomad4 AMR AF: 0.644

Gnomad4 ASJ AF: 0.543

Gnomad4 EAS AF: 0.642

Gnomad4 SAS AF: 0.632

Gnomad4 FIN AF: 0.653

Gnomad4 NFE AF: 0.565

Gnomad4 OTH AF: 0.639

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

- -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

- -

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs58188320; hg19: chr21-46931004;