rs793494

Positions:

• chr3-99789924-T-C
• chr3-99789924-T-G

Variant summary

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

The NM_020351.4(COL8A1):​c.-3-756T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,134 control chromosomes in the GnomAD database, including 42,375 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 0.74 (42375 hom., cov: 32)
• Consequence: COL8A1 NM_020351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.317

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 (AFR) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL8A1	NM_020351.4	c.-3-756T>C		intron_variant		ENST00000652472.1	NP_065084.2
COL8A1	NM_001850.5	c.-3-756T>C		intron_variant			NP_001841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL8A1	ENST00000652472.1	c.-3-756T>C		intron_variant			NM_020351.4	ENSP00000498483	P1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112619 AN: 152016 Hom.: 42335 Cov.: 32

Gnomad AFR AF: 0.878

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.750

Gnomad EAS AF: 0.812

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.730

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

GnomAD4 genome AF: 0.741 AC: 112711 AN: 152134 Hom.: 42375 Cov.: 32 AF XY: 0.737 AC XY: 54780 AN XY: 74374

Gnomad4 AFR AF: 0.878

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.750

Gnomad4 EAS AF: 0.812

Gnomad4 SAS AF: 0.687

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.729

Alfa AF: 0.699 Hom.: 16629

Bravo AF: 0.748

Asia WGS AF: 0.740 AC: 2575 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	1.9
DANN	Benign	0.64

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: rs793494; hg19: chr3-99508768;