Genetic Variant COL28A1:p.Gly1066Glu (chr7-7360398-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001037763.3(COL28A1):c.3197G>A(p.Gly1066Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00047 in 1,573,844 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00049 ( 1 hom. )

Consequence

COL28A1
NM_001037763.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0810

Publications

2 publications found

Variant links:

Genes affected

COL28A1 (HGNC:22442): (collagen type XXVIII alpha 1 chain) COL28A1 belongs to a class of collagens containing von Willebrand factor (VWF; MIM 613160) type A (VWFA) domains (Veit et al., 2006 [PubMed 16330543]).[supplied by OMIM, Nov 2010]

COL28A1 links:

LOC107986764 (HGNC:):

LOC107986764 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.060524166).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037763.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL28A1	NM_001037763.3	MANE Select	c.3197G>A	p.Gly1066Glu	missense	Exon 34 of 35	NP_001032852.2	Q2UY09-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL28A1	ENST00000399429.8	TSL:1 MANE Select	c.3197G>A	p.Gly1066Glu	missense	Exon 34 of 35	ENSP00000382356.3	Q2UY09-1
COL28A1	ENST00000453441.1	TSL:2	c.62G>A	p.Gly21Glu	missense	Exon 1 of 3	ENSP00000391380.1	H7BZU0
COL28A1	ENST00000430711.5	TSL:5	n.248G>A		non_coding_transcript_exon	Exon 2 of 4	ENSP00000413093.1	H7C3P2

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000193

AC:

AN:

212512

AF XY:

0.000207

show subpopulations

Gnomad AFR exome

AF:

0.000141

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000368

Gnomad OTH exome

AF:

0.000203

GnomAD4 exome

AF:

0.000487

AC:

692

AN:

1421680

Hom.:

Cov.:

AF XY:

0.000452

AC XY:

319

AN XY:

706000

show subpopulations

African (AFR)

AF:

0.000162

AC:

AN:

30886

American (AMR)

AF:

0.00

AC:

AN:

32750

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24618

East Asian (EAS)

AF:

0.00

AC:

AN:

38204

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79056

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.000568

AC:

624

AN:

1098768

Other (OTH)

AF:

0.00104

AC:

AN:

58722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000315

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0000964

AC:

AN:

41510

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5166

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000647

AC:

AN:

68010

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000540

Hom.:

Bravo

AF:

0.000257

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000722

AC:

ExAC

AF:

0.000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.42

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.0032

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.42

M_CAP

Benign

0.011

MetaRNN

Benign

0.061

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.0

PhyloP100

0.081

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.6

REVEL

Benign

0.11

Sift

Benign

0.32

Sift4G

Benign

0.79

Polyphen

0.029

Vest4

0.14

MVP

0.13

MPC

0.033

ClinPred

0.021

GERP RS

-0.12

PromoterAI

0.039

Neutral

(source)

Varity_R

0.080

gMVP

0.28

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over