21-45405299-G-C

Position:

• chr21-45405299-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001379500.1(COL18A1):​c.11+58G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (6321 hom., cov: 0)
  • Exomes 𝑓: 0.47 (39707 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0500

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]

BNAT1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 21-45405299-G-C is Benign according to our data. Variant chr21-45405299-G-C is described in ClinVar as [Benign]. Clinvar id is 1277646.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL18A1	NM_001379500.1	c.11+58G>C		intron_variant		ENST00000651438.1
BNAT1	NR_183526.1	n.197-803C>G		intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1	n.181+61C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.11+58G>C		intron_variant			NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 41287 AN: 72650 Hom.: 6317 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.547

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.558

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.579

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.575

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.473 AC: 195496 AN: 413696 Hom.: 39707 Cov.: 5 AF XY: 0.473 AC XY: 94836 AN XY: 200536

Gnomad4 AFR exome AF: 0.375

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.491

Gnomad4 EAS exome AF: 0.360

Gnomad4 SAS exome AF: 0.534

Gnomad4 FIN exome AF: 0.454

Gnomad4 NFE exome AF: 0.480

Gnomad4 OTH exome AF: 0.457

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.568 AC: 41294 AN: 72660 Hom.: 6321 Cov.: 0 AF XY: 0.569 AC XY: 19885 AN XY: 34962

Gnomad4 AFR AF: 0.547

Gnomad4 AMR AF: 0.558

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.582

Gnomad4 FIN AF: 0.579

Gnomad4 NFE AF: 0.581

Gnomad4 OTH AF: 0.579

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 10, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.4
DANN	Benign	0.13

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs113272297; hg19: chr21-46825214;