Genetic Variant COL28A1:p.Gln882Leu (chr7-7373261-T-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001037763.3(COL28A1):c.2645A>T(p.Gln882Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00394 in 1,614,184 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 140 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 102 hom. )

Consequence

COL28A1
NM_001037763.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.13

Publications

4 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: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002996266).

BP6

Variant 7-7373261-T-A is Benign according to our data. Variant chr7-7373261-T-A is described in ClinVar as Benign. ClinVar VariationId is 776204.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0735 is higher than 0.05.

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.2645A>T	p.Gln882Leu	missense	Exon 32 of 35	NP_001032852.2	Q2UY09-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL28A1	ENST00000399429.8	TSL:1 MANE Select	c.2645A>T	p.Gln882Leu	missense	Exon 32 of 35	ENSP00000382356.3	Q2UY09-1

Frequencies

GnomAD3 genomes

AF:

0.0216

AC:

3286

AN:

152172

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0758

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00628

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.00527

AC:

1316

AN:

249526

AF XY:

0.00403

show subpopulations

Gnomad AFR exome

AF:

0.0750

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000221

Gnomad OTH exome

AF:

0.00281

GnomAD4 exome

AF:

0.00210

AC:

3076

AN:

1461894

Hom.:

102

Cov.:

AF XY:

0.00180

AC XY:

1308

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.0747

AC:

2501

AN:

33480

American (AMR)

AF:

0.00380

AC:

170

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00329

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000944

AC:

105

AN:

1112012

Other (OTH)

AF:

0.00445

AC:

269

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

197

394

590

787

984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

164

246

328

410

<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:

0.0216

AC:

3290

AN:

152290

Hom.:

140

Cov.:

AF XY:

0.0204

AC XY:

1519

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0758

AC:

3147

AN:

41542

American (AMR)

AF:

0.00621

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000265

AC:

AN:

68024

Other (OTH)

AF:

0.0132

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

152

304

457

609

761

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.00325

Hom.:

Bravo

AF:

0.0232

ESP6500AA

AF:

0.0659

AC:

266

ESP6500EA

AF:

0.000239

AC:

ExAC

AF:

0.00651

AC:

787

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.038

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.0034

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.83

MutationAssessor

Benign

1.7

PhyloP100

4.1

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.31

Sift

Benign

0.12

Sift4G

Uncertain

0.035

Polyphen

0.10

Vest4

0.35

MVP

0.41

MPC

0.031

ClinPred

0.027

GERP RS

4.3

Varity_R

0.18

gMVP

0.53

Mutation Taster

=89/11

polymorphism (auto)

(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