chr21-45405308-G-C

Position:

• chr21-45405308-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+67G>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 0.60 (10141 hom., cov: 17)
  • Exomes 𝑓: 0.57 (54406 hom.)
  • Failed GnomAD Quality Control
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.379

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=-0.92).
• BP6: Variant 21-45405308-G-C is Benign according to our data. Variant chr21-45405308-G-C is described in ClinVar as [Benign]. Clinvar id is 1268095.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+67G>C		intron_variant		ENST00000651438.1
BNAT1	NR_183526.1	n.197-812C>G		intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1	n.181+52C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.11+67G>C		intron_variant			NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 52717 AN: 88214 Hom.: 10139 Cov.: 17 FAILED QC

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.593

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.592

Gnomad FIN AF: 0.581

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.595

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.575 AC: 259848 AN: 451970 Hom.: 54406 Cov.: 5 AF XY: 0.575 AC XY: 124928 AN XY: 217402

Gnomad4 AFR exome AF: 0.616

Gnomad4 AMR exome AF: 0.486

Gnomad4 ASJ exome AF: 0.559

Gnomad4 EAS exome AF: 0.397

Gnomad4 SAS exome AF: 0.584

Gnomad4 FIN exome AF: 0.523

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.565

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.598 AC: 52739 AN: 88258 Hom.: 10141 Cov.: 17 AF XY: 0.596 AC XY: 25239 AN XY: 42360

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.593

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.581

Gnomad4 NFE AF: 0.596

Gnomad4 OTH AF: 0.597

Alfa AF: 0.433 Hom.: 99

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.1
DANN	Benign	0.12

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs60499034; hg19: chr21-46825223;