3-99762695-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020351.4(COL8A1):c.-4+17674G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 152,282 control chromosomes in the GnomAD database, including 583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.080 (583 hom., cov: 32)
• Consequence: COL8A1 NM_020351.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.14

Genes affected

COL8A1 (HGNC:2215): (collagen type VIII alpha 1 chain) This gene encodes one of the two alpha chains of type VIII collagen. The gene product is a short chain collagen and a major component of the basement membrane of the corneal endothelium. The type VIII collagen fibril can be either a homo- or a heterotrimer. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL8A1	NM_020351.4	c.-4+17674G>T		intron_variant		ENST00000652472.1
COL8A1	NM_001850.5	c.-4+17674G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL8A1	ENST00000652472.1	c.-4+17674G>T		intron_variant			NM_020351.4	P1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12142 AN: 152164 Hom.: 584 Cov.: 32

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.0331

Gnomad SAS AF: 0.0903

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0968

Gnomad OTH AF: 0.0690

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0797 AC: 12131 AN: 152282 Hom.: 583 Cov.: 32 AF XY: 0.0815 AC XY: 6070 AN XY: 74456

Gnomad4 AFR AF: 0.0454

Gnomad4 AMR AF: 0.0518

Gnomad4 ASJ AF: 0.0378

Gnomad4 EAS AF: 0.0326

Gnomad4 SAS AF: 0.0899

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.0968

Gnomad4 OTH AF: 0.0678

Alfa AF: 0.0891 Hom.: 1149

Bravo AF: 0.0683

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

not provided

Department of Ophthalmology and Visual Sciences Kyoto University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.49
Dann	Benign	0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs13081855; hg19: chr3-99481539;