chr21-45405221-TG-T

Position:

• chr21-45405221-TG-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001379500.1(COL18A1):​c.-6del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0017 (1 hom.)
• Consequence: COL18A1 NM_001379500.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.965

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 21-45405221-TG-T is Benign according to our data. Variant chr21-45405221-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 2652790.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr21-45405221-TG-T is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL18A1	NM_001379500.1	c.-6del		5_prime_UTR_variant	1/42	ENST00000651438.1
BNAT1	NR_183526.1	n.197-726del		intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1	n.181+138del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.-6del		5_prime_UTR_variant	1/42		NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.00118 AC: 61 AN: 51900 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000872

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000362

Gnomad ASJ AF: 0.0306

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0116

Gnomad NFE AF: 0.000674

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00136 AC: 6 AN: 4428 Hom.: 0 AF XY: 0.00148 AC XY: 4 AN XY: 2704

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.0108

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00238

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00168 AC: 143 AN: 84934 Hom.: 1 Cov.: 1 AF XY: 0.00153 AC XY: 69 AN XY: 45078

Gnomad4 AFR exome AF: 0.00162

Gnomad4 AMR exome AF: 0.00314

Gnomad4 ASJ exome AF: 0.0260

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000578

Gnomad4 OTH exome AF: 0.00300

GnomAD4 genome AF: 0.00117 AC: 61 AN: 51964 Hom.: 0 Cov.: 0 AF XY: 0.00137 AC XY: 35 AN XY: 25498

Gnomad4 AFR AF: 0.0000869

Gnomad4 AMR AF: 0.000361

Gnomad4 ASJ AF: 0.0306

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000674

Gnomad4 OTH AF: 0.00420

Alfa AF: 0.000356 Hom.: 0

Bravo AF: 0.000563

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

COL18A1: BP4 -

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: rs763620362; hg19: chr21-46825136;