21-45405320-C-T

Position:

• chr21-45405320-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001379500.1(COL18A1):​c.12-59C>T 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 0.080 (87 hom., cov: 0)
  • Exomes 𝑓: 0.015 (98 hom.)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.26

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 21-45405320-C-T is Benign according to our data. Variant chr21-45405320-C-T is described in ClinVar as [Benign]. Clinvar id is 1277766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL18A1	NM_001379500.1	c.12-59C>T		intron_variant		ENST00000651438.1
BNAT1	NR_183526.1	n.197-824G>A		intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1	n.181+40G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.12-59C>T		intron_variant			NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.0796 AC: 3076 AN: 38644 Hom.: 86 Cov.: 0

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0379

Gnomad ASJ AF: 0.00615

Gnomad EAS AF: 0.0630

Gnomad SAS AF: 0.0733

Gnomad FIN AF: 0.0430

Gnomad MID AF: 0.0513

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0649

GnomAD4 exome AF: 0.0151 AC: 5118 AN: 338368 Hom.: 98 Cov.: 4 AF XY: 0.0146 AC XY: 2353 AN XY: 161450

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.0261

Gnomad4 ASJ exome AF: 0.00649

Gnomad4 EAS exome AF: 0.0396

Gnomad4 SAS exome AF: 0.0222

Gnomad4 FIN exome AF: 0.0284

Gnomad4 NFE exome AF: 0.00994

Gnomad4 OTH exome AF: 0.0250

GnomAD4 genome AF: 0.0796 AC: 3081 AN: 38682 Hom.: 87 Cov.: 0 AF XY: 0.0773 AC XY: 1468 AN XY: 18980

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.00615

Gnomad4 EAS AF: 0.0626

Gnomad4 SAS AF: 0.0738

Gnomad4 FIN AF: 0.0430

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.0633

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	-0.84
CADD	Benign	7.5
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs185357103; hg19: chr21-46825235;