rs17778253

Positions:

• chr3-99716258-T-C

Variant summary

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

The NM_020351.4(COL8A1):​c.-128-28639T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 151,978 control chromosomes in the GnomAD database, including 1,297 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 0.12 (1297 hom., cov: 32)
• Consequence: COL8A1 NM_020351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL8A1	NM_020351.4	c.-128-28639T>C		intron_variant		ENST00000652472.1	NP_065084.2
COL8A1	NM_001850.5	c.-128-28639T>C		intron_variant			NP_001841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL8A1	ENST00000652472.1	c.-128-28639T>C		intron_variant			NM_020351.4	ENSP00000498483	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18024 AN: 151860 Hom.: 1284 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0724

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.0340

Gnomad SAS AF: 0.0764

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.119 AC: 18060 AN: 151978 Hom.: 1297 Cov.: 32 AF XY: 0.119 AC XY: 8850 AN XY: 74268

Gnomad4 AFR AF: 0.180

Gnomad4 AMR AF: 0.0723

Gnomad4 ASJ AF: 0.0398

Gnomad4 EAS AF: 0.0335

Gnomad4 SAS AF: 0.0761

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.0976

Gnomad4 OTH AF: 0.100

Alfa AF: 0.0956 Hom.: 1037

Bravo AF: 0.113

Asia WGS AF: 0.0650 AC: 227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.36

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: rs17778253; hg19: chr3-99435102;