3-99757451-C-T

Position:

• chr3-99757451-C-T

Variant summary

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

The NM_020351.4(COL8A1):​c.-4+12430C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 151,874 control chromosomes in the GnomAD database, including 20,156 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 0.51 (20156 hom., cov: 31)
• Consequence: COL8A1 NM_020351.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0460

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 (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COL8A1	NM_020351.4	c.-4+12430C>T		intron_variant		ENST00000652472.1	NP_065084.2
COL8A1	NM_001850.5	c.-4+12430C>T		intron_variant			NP_001841.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COL8A1	ENST00000652472.1	c.-4+12430C>T		intron_variant			NM_020351.4	ENSP00000498483.1

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77712 AN: 151756 Hom.: 20135 Cov.: 31

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.512 AC: 77778 AN: 151874 Hom.: 20156 Cov.: 31 AF XY: 0.509 AC XY: 37752 AN XY: 74180

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.518

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.497

Gnomad4 OTH AF: 0.538

Alfa AF: 0.513 Hom.: 40833

Bravo AF: 0.524

Asia WGS AF: 0.547 AC: 1904 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	1.0
DANN	Benign	0.42

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: rs792835; hg19: chr3-99476295;