rs669676

chr3-99730008-A-Gchr3-99730008-A-T

Variant summary

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

The NM_020351.4(COL8A1):c.-128-14889A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 151,982 control chromosomes in the GnomAD database, including 16,243 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.46 (16243 hom., cov: 32)
• Consequence: COL8A1 NM_020351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL8A1	NM_020351.4	c.-128-14889A>G		intron_variant		ENST00000652472.1
COL8A1	NM_001850.5	c.-128-14889A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL8A1	ENST00000652472.1	c.-128-14889A>G		intron_variant			NM_020351.4	P1

Frequencies

GnomAD3 genomes AF: 0.457 AC: 69401 AN: 151864 Hom.: 16236 Cov.: 32

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.633

Gnomad SAS AF: 0.427

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.457 AC: 69437 AN: 151982 Hom.: 16243 Cov.: 32 AF XY: 0.453 AC XY: 33619 AN XY: 74268

Gnomad4 AFR AF: 0.412

Gnomad4 AMR AF: 0.487

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.633

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.364

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.489

Alfa AF: 0.465 Hom.: 2831

Bravo AF: 0.470

Asia WGS AF: 0.504 AC: 1755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	9.2
Dann	Benign	0.81

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: rs669676; hg19: chr3-99448852;