NM_020351.4:c.-129+38764T>C

Variant names:

• chr3-99677428-T-C
• rs13095226
• NM_020351.4:c.-129+38764T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020351.4(COL8A1):​c.-129+38764T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0953 in 152,142 control chromosomes in the GnomAD database, including 858 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 0.095 (858 hom., cov: 32)
• Consequence: COL8A1 NM_020351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09
• Publications: 38 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A1	NM_020351.4	c.-129+38764T>C		intron_variant	Intron 1 of 3	ENST00000652472.1	NP_065084.2
COL8A1	NM_001850.5	c.-129+1707T>C		intron_variant	Intron 2 of 4		NP_001841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL8A1	ENST00000652472.1	c.-129+38764T>C		intron_variant	Intron 1 of 3		NM_020351.4	ENSP00000498483.1

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14507 AN: 152024 Hom.: 860 Cov.: 32

Gnomad AFR AF: 0.0511

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0793

Gnomad ASJ AF: 0.0712

Gnomad EAS AF: 0.0619

Gnomad SAS AF: 0.0809

Gnomad FIN AF: 0.229

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0799

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

GnomAD4 genome AF: 0.0953 AC: 14499 AN: 152142 Hom.: 858 Cov.: 32 AF XY: 0.0986 AC XY: 7333 AN XY: 74364

African (AFR) AF: 0.0510 AC: 2116 AN: 41526

American (AMR) AF: 0.0793 AC: 1212 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0712 AC: 247 AN: 3470

East Asian (EAS) AF: 0.0614 AC: 318 AN: 5176

South Asian (SAS) AF: 0.0805 AC: 388 AN: 4818

European-Finnish (FIN) AF: 0.229 AC: 2428 AN: 10582

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7421 AN: 67972

Other (OTH) AF: 0.0791 AC: 167 AN: 2112

Alfa AF: 0.101 Hom.: 1703

Bravo AF: 0.0840

Asia WGS AF: 0.0670 AC: 235 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.74
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: rs13095226; hg19: chr3-99396272;