Variant 3-99795506-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020351.4(COL8A1):c.1605C>T(p.Pro535=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,588,242 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0050 ( 19 hom. )

Consequence

COL8A1
NM_020351.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.95

Variant links:

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]

COL8A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 3-99795506-C-T is Benign according to our data. Variant chr3-99795506-C-T is described in ClinVar as [Benign]. Clinvar id is 784470.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-2.95 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL8A1	NM_020351.4 linkuse as main transcript	c.1605C>T	p.Pro535=	synonymous_variant	4/4	ENST00000652472.1
COL8A1	NM_001850.5 linkuse as main transcript	c.1605C>T	p.Pro535=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
COL8A1	ENST00000652472.1 linkuse as main transcript	c.1605C>T	p.Pro535=	synonymous_variant	4/4		NM_020351.4	P1
COL8A1	ENST00000261037.7 linkuse as main transcript	c.1605C>T	p.Pro535=	synonymous_variant	5/5	1		P1
COL8A1	ENST00000273342.8 linkuse as main transcript	c.1605C>T	p.Pro535=	synonymous_variant	4/4	2		P1

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

559

AN:

151580

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000993

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.000578

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00536

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00380

AC:

794

AN:

209012

Hom.:

AF XY:

0.00380

AC XY:

433

AN XY:

114048

show subpopulations

Gnomad AFR exome

AF:

0.000802

Gnomad AMR exome

AF:

0.00290

Gnomad ASJ exome

AF:

0.000441

Gnomad EAS exome

AF:

0.0000649

Gnomad SAS exome

AF:

0.00176

Gnomad FIN exome

AF:

0.0103

Gnomad NFE exome

AF:

0.00456

Gnomad OTH exome

AF:

0.00760

GnomAD4 exome

AF:

0.00496

AC:

7123

AN:

1436544

Hom.:

Cov.:

AF XY:

0.00481

AC XY:

3429

AN XY:

712330

show subpopulations

Gnomad4 AFR exome

AF:

0.000762

Gnomad4 AMR exome

AF:

0.00317

Gnomad4 ASJ exome

AF:

0.000352

Gnomad4 EAS exome

AF:

0.0000261

Gnomad4 SAS exome

AF:

0.00212

Gnomad4 FIN exome

AF:

0.0106

Gnomad4 NFE exome

AF:

0.00542

Gnomad4 OTH exome

AF:

0.00460

GnomAD4 genome

AF:

0.00368

AC:

559

AN:

151698

Hom.:

Cov.:

AF XY:

0.00374

AC XY:

277

AN XY:

74120

show subpopulations

Gnomad4 AFR

AF:

0.000990

Gnomad4 AMR

AF:

0.00151

Gnomad4 ASJ

AF:

0.000578

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00125

Gnomad4 FIN

AF:

0.0111

Gnomad4 NFE

AF:

0.00536

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00382

Hom.:

Bravo

AF:

0.00284

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.19

DANN

Benign

0.29

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over