chr3-99730008-A-G

Variant names:

• chr3-99730008-A-G
• rs669676
• NM_020351.4:c.-128-14889A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

ENSG00000296790 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020351.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL8A1	NM_020351.4	MANE Select	c.-128-14889A>G		intron	N/A	NP_065084.2
	COL8A1	NM_001850.5		c.-128-14889A>G		intron	N/A	NP_001841.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL8A1	ENST00000652472.1	MANE Select	c.-128-14889A>G		intron	N/A	ENSP00000498483.1	P27658
	COL8A1	ENST00000261037.7	TSL:1	c.-128-14889A>G		intron	N/A	ENSP00000261037.3	P27658
	COL8A1	ENST00000895751.1		c.-128-14889A>G		intron	N/A	ENSP00000565810.1

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

African (AFR) AF: 0.412 AC: 17077 AN: 41466

American (AMR) AF: 0.487 AC: 7427 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.660 AC: 2289 AN: 3470

East Asian (EAS) AF: 0.633 AC: 3266 AN: 5156

South Asian (SAS) AF: 0.426 AC: 2055 AN: 4822

European-Finnish (FIN) AF: 0.364 AC: 3844 AN: 10560

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31837 AN: 67952

Other (OTH) AF: 0.489 AC: 1032 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.2
DANN	Benign	0.81
PhyloP100		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs669676; hg19: chr3-99448852;