chr21-45405319-C-CTGGGT

Position:

• chr21-45405319-C-CTGGGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001379500.1(COL18A1):​c.12-60_12-59insTGGGT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (274 hom., cov: 0)
  • Exomes 𝑓: 0.026 (395 hom.)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 21-45405319-C-CTGGGT is Benign according to our data. Variant chr21-45405319-C-CTGGGT is described in ClinVar as [Benign]. Clinvar id is 1276294.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL18A1	NM_001379500.1	c.12-60_12-59insTGGGT		intron_variant		ENST00000651438.1
BNAT1	NR_183526.1	n.197-824_197-823insACCCA		intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1	n.181+40_181+41insACCCA		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.12-60_12-59insTGGGT		intron_variant			NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 6035 AN: 98690 Hom.: 271 Cov.: 0

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.00351

Gnomad AMR AF: 0.0339

Gnomad ASJ AF: 0.0326

Gnomad EAS AF: 0.00510

Gnomad SAS AF: 0.0740

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.113

Gnomad NFE AF: 0.0288

Gnomad OTH AF: 0.0609

GnomAD4 exome AF: 0.0261 AC: 17447 AN: 668404 Hom.: 395 Cov.: 4 AF XY: 0.0259 AC XY: 8316 AN XY: 320996

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.0214

Gnomad4 ASJ exome AF: 0.0303

Gnomad4 EAS exome AF: 0.0203

Gnomad4 SAS exome AF: 0.0545

Gnomad4 FIN exome AF: 0.0121

Gnomad4 NFE exome AF: 0.0237

Gnomad4 OTH exome AF: 0.0297

GnomAD4 genome AF: 0.0611 AC: 6036 AN: 98754 Hom.: 274 Cov.: 0 AF XY: 0.0598 AC XY: 2899 AN XY: 48488

Gnomad4 AFR AF: 0.169

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.0326

Gnomad4 EAS AF: 0.00512

Gnomad4 SAS AF: 0.0731

Gnomad4 FIN AF: 0.0172

Gnomad4 NFE AF: 0.0288

Gnomad4 OTH AF: 0.0601

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 11, 2021

- -

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: rs1491324273; hg19: chr21-46825234;