21-45405314-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001379500.1(COL18A1):c.12-65C>G 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 0.23 (585 hom., cov: 0)
  • Exomes 𝑓: 0.067 (660 hom.)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.393

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 21-45405314-C-G is Benign according to our data. Variant chr21-45405314-C-G is described in ClinVar as [Benign]. Clinvar id is 1253503.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL18A1	NM_001379500.1	c.12-65C>G		intron_variant		ENST00000651438.1
BNAT1	NR_183526.1	n.197-818G>C		intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1	n.181+46G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.12-65C>G		intron_variant			NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 8718 AN: 37540 Hom.: 580 Cov.: 0

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.0507

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0258

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.0994

Gnomad MID AF: 0.308

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.250

GnomAD4 exome AF: 0.0673 AC: 21679 AN: 322198 Hom.: 660 Cov.: 4 AF XY: 0.0670 AC XY: 10300 AN XY: 153680

Gnomad4 AFR exome AF: 0.345

Gnomad4 AMR exome AF: 0.0724

Gnomad4 ASJ exome AF: 0.0812

Gnomad4 EAS exome AF: 0.0637

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.0595

Gnomad4 NFE exome AF: 0.0579

Gnomad4 OTH exome AF: 0.0857

GnomAD4 genome AF: 0.232 AC: 8725 AN: 37570 Hom.: 585 Cov.: 0 AF XY: 0.229 AC XY: 4177 AN XY: 18262

Gnomad4 AFR AF: 0.456

Gnomad4 AMR AF: 0.132

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0259

Gnomad4 SAS AF: 0.251

Gnomad4 FIN AF: 0.0994

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.244

Alfa AF: 0.125 Hom.: 4

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.91
Cadd	Benign	1.8
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: rs879335792; hg19: chr21-46825229; COSMIC: COSV68496685; COSMIC: COSV68496685;