chr3-99762695-G-T

Variant names:

• chr3-99762695-G-T
• rs13081855
• NM_020351.4:c.-4+17674G>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+17674G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0797 in 152,282 control chromosomes in the GnomAD database, including 583 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: 𝑓 0.080 (583 hom., cov: 32)
• Consequence: COL8A1 NM_020351.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.14
• Publications: 37 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A1	NM_020351.4	c.-4+17674G>T		intron_variant	Intron 2 of 3	ENST00000652472.1	NP_065084.2
COL8A1	NM_001850.5	c.-4+17674G>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+17674G>T		intron_variant	Intron 2 of 3		NM_020351.4	ENSP00000498483.1

Frequencies

GnomAD3 genomes AF: 0.0798 AC: 12142 AN: 152164 Hom.: 584 Cov.: 32

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.0331

Gnomad SAS AF: 0.0903

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0968

Gnomad OTH AF: 0.0690

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

GnomAD4 genome AF: 0.0797 AC: 12131 AN: 152282 Hom.: 583 Cov.: 32 AF XY: 0.0815 AC XY: 6070 AN XY: 74456

African (AFR) AF: 0.0454 AC: 1889 AN: 41568

American (AMR) AF: 0.0518 AC: 793 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3468

East Asian (EAS) AF: 0.0326 AC: 169 AN: 5182

South Asian (SAS) AF: 0.0899 AC: 434 AN: 4826

European-Finnish (FIN) AF: 0.169 AC: 1788 AN: 10608

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0968 AC: 6583 AN: 68016

Other (OTH) AF: 0.0678 AC: 143 AN: 2110

Alfa AF: 0.0859 Hom.: 2372

Bravo AF: 0.0683

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

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Department of Ophthalmology and Visual Sciences Kyoto University

Significance: not provided

Review Status: no classification provided

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.58
PhyloP100		-1.1
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: rs13081855; hg19: chr3-99481539;