3-99756424-C-T

Variant names:

• chr3-99756424-C-T
• rs792833
• NM_020351.4:c.-4+11403C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020351.4(COL8A1):​c.-4+11403C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,860 control chromosomes in the GnomAD database, including 20,140 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 0.51 (20140 hom., cov: 32)
• Consequence: COL8A1 NM_020351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.747
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A1	NM_020351.4	c.-4+11403C>T		intron_variant	Intron 2 of 3	ENST00000652472.1	NP_065084.2
COL8A1	NM_001850.5	c.-4+11403C>T		intron_variant	Intron 3 of 4		NP_001841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL8A1	ENST00000652472.1	c.-4+11403C>T		intron_variant	Intron 2 of 3		NM_020351.4	ENSP00000498483.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77708 AN: 151742 Hom.: 20119 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.537

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

GnomAD4 genome AF: 0.512 AC: 77774 AN: 151860 Hom.: 20140 Cov.: 32 AF XY: 0.509 AC XY: 37768 AN XY: 74200

African (AFR) AF: 0.525 AC: 21726 AN: 41386

American (AMR) AF: 0.518 AC: 7896 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2327 AN: 3468

East Asian (EAS) AF: 0.668 AC: 3451 AN: 5166

South Asian (SAS) AF: 0.460 AC: 2217 AN: 4818

European-Finnish (FIN) AF: 0.443 AC: 4663 AN: 10520

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33754 AN: 67944

Other (OTH) AF: 0.538 AC: 1138 AN: 2114

Alfa AF: 0.425 Hom.: 1850

Bravo AF: 0.524

Asia WGS AF: 0.547 AC: 1904 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.40
PhyloP100		0.75
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: rs792833; hg19: chr3-99475268;