3-99777507-G-T

Variant names:

• chr3-99777507-G-T
• rs7614366
• NM_020351.4:c.-3-13173G>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.-3-13173G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,048 control chromosomes in the GnomAD database, including 4,045 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 0.22 (4045 hom., cov: 32)
• Consequence: COL8A1 NM_020351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.584
• Publications: 4 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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL8A1	NM_020351.4	c.-3-13173G>T		intron_variant	Intron 2 of 3	ENST00000652472.1	NP_065084.2
COL8A1	NM_001850.5	c.-3-13173G>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.-3-13173G>T		intron_variant	Intron 2 of 3		NM_020351.4	ENSP00000498483.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32762 AN: 151928 Hom.: 4035 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0796

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.258

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.216 AC: 32788 AN: 152048 Hom.: 4045 Cov.: 32 AF XY: 0.218 AC XY: 16190 AN XY: 74342

African (AFR) AF: 0.331 AC: 13736 AN: 41458

American (AMR) AF: 0.135 AC: 2066 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0796 AC: 276 AN: 3468

East Asian (EAS) AF: 0.115 AC: 593 AN: 5168

South Asian (SAS) AF: 0.242 AC: 1163 AN: 4814

European-Finnish (FIN) AF: 0.258 AC: 2727 AN: 10570

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11568 AN: 67970

Other (OTH) AF: 0.181 AC: 383 AN: 2114

Alfa AF: 0.162 Hom.: 1132

Bravo AF: 0.208

Asia WGS AF: 0.187 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	2.6
DANN	Benign	0.50
PhyloP100		-0.58
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: rs7614366; hg19: chr3-99496351;