chr21-45405327-TGCGGGGGTC-T

Position:

• chr21-45405327-TGCGGGGGTC-T

Variant summary

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

The NM_001379500.1(COL18A1):​c.12-42_12-34del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00348 in 1,026,506 control chromosomes in the GnomAD database, including 108 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (59 hom., cov: 0)
  • Exomes 𝑓: 0.0016 (49 hom.)
• Consequence: COL18A1 NM_001379500.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.460

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 21-45405327-TGCGGGGGTC-T is Benign according to our data. Variant chr21-45405327-TGCGGGGGTC-T is described in ClinVar as [Benign]. Clinvar id is 1277042.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL18A1	NM_001379500.1	c.12-42_12-34del		intron_variant		ENST00000651438.1
BNAT1	NR_183526.1	n.196+831_197-832del		intron_variant, non_coding_transcript_variant
BNAT1	NR_183527.1	n.181+24_181+32del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL18A1	ENST00000651438.1	c.12-42_12-34del		intron_variant			NM_001379500.1

Frequencies

GnomAD3 genomes AF: 0.0159 AC: 2111 AN: 133036 Hom.: 58 Cov.: 0

Gnomad AFR AF: 0.0574

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00596

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000724

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00746

Gnomad NFE AF: 0.000262

Gnomad OTH AF: 0.0136

GnomAD4 exome AF: 0.00162 AC: 1451 AN: 893378 Hom.: 49 AF XY: 0.00148 AC XY: 634 AN XY: 427022

Gnomad4 AFR exome AF: 0.0561

Gnomad4 AMR exome AF: 0.00723

Gnomad4 ASJ exome AF: 0.0000886

Gnomad4 EAS exome AF: 0.0000997

Gnomad4 SAS exome AF: 0.00123

Gnomad4 FIN exome AF: 0.0000508

Gnomad4 NFE exome AF: 0.000281

Gnomad4 OTH exome AF: 0.00414

GnomAD4 genome AF: 0.0159 AC: 2119 AN: 133128 Hom.: 59 Cov.: 0 AF XY: 0.0149 AC XY: 970 AN XY: 64962

Gnomad4 AFR AF: 0.0574

Gnomad4 AMR AF: 0.00595

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000725

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000262

Gnomad4 OTH AF: 0.0135

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: rs1387248324; hg19: chr21-46825242;