3-99757540-G-T

Variant names:

• chr3-99757540-G-T
• rs792836
• NM_020351.4:c.-4+12519G>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+12519G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 151,944 control chromosomes in the GnomAD database, including 20,182 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 (20182 hom., cov: 32)
• Consequence: COL8A1 NM_020351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A1	NM_020351.4	c.-4+12519G>T		intron_variant	Intron 2 of 3	ENST00000652472.1	NP_065084.2
COL8A1	NM_001850.5	c.-4+12519G>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+12519G>T		intron_variant	Intron 2 of 3		NM_020351.4	ENSP00000498483.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77811 AN: 151828 Hom.: 20161 Cov.: 32

Gnomad AFR AF: 0.526

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.513 AC: 77877 AN: 151944 Hom.: 20182 Cov.: 32 AF XY: 0.509 AC XY: 37823 AN XY: 74248

Gnomad4 AFR AF: 0.526

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.538

Alfa AF: 0.337 Hom.: 787

Bravo AF: 0.525

Asia WGS AF: 0.547 AC: 1904 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.12
DANN	Benign	0.42

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: rs792836; hg19: chr3-99476384;