3-99769388-T-C

Variant names:

• chr3-99769388-T-C
• rs793479
• NM_020351.4:c.-3-21292T>C

Variant summary

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

The NM_020351.4(COL8A1):​c.-3-21292T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 152,128 control chromosomes in the GnomAD database, including 31,950 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 0.64 (31950 hom., cov: 32)
• Consequence: COL8A1 NM_020351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A1	NM_020351.4	c.-3-21292T>C		intron_variant	Intron 2 of 3	ENST00000652472.1	NP_065084.2
COL8A1	NM_001850.5	c.-3-21292T>C		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.-3-21292T>C		intron_variant	Intron 2 of 3		NM_020351.4	ENSP00000498483.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97321 AN: 152010 Hom.: 31911 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.646

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

GnomAD4 genome AF: 0.640 AC: 97419 AN: 152128 Hom.: 31950 Cov.: 32 AF XY: 0.638 AC XY: 47431 AN XY: 74352

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.713

Gnomad4 EAS AF: 0.755

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.646

Alfa AF: 0.449 Hom.: 1075

Bravo AF: 0.655

Asia WGS AF: 0.677 AC: 2356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.73

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: rs793479; hg19: chr3-99488232;