Genetic Variant COL28A1:p.Gln80Gln (chr7-7531789-T-C) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001037763.3(COL28A1):c.240A>G(p.Gln80Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00426 in 1,605,212 control chromosomes in the GnomAD database, including 243 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.022 ( 146 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 97 hom. )

Consequence

COL28A1
NM_001037763.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.93

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BP6

Variant 7-7531789-T-C is Benign according to our data. Variant chr7-7531789-T-C is described in ClinVar as Benign. ClinVar VariationId is 776205.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COL28A1	NM_001037763.3 link	c.240A>G	p.Gln80Gln	synonymous_variant	Exon 3 of 35	ENST00000399429.8	NP_001032852.2	Q2UY09-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COL28A1	ENST00000399429.8 link	c.240A>G	p.Gln80Gln	synonymous_variant	Exon 3 of 35	1	NM_001037763.3	ENSP00000382356.3		Q2UY09-1

Frequencies

GnomAD3 genomes

AF:

0.0219

AC:

3329

AN:

152186

Hom.:

147

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0761

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00779

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0143

GnomAD2 exomes

AF:

0.00573

AC:

1426

AN:

248946

AF XY:

0.00455

show subpopulations

Gnomad AFR exome

AF:

0.0785

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.000111

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000293

Gnomad OTH exome

AF:

0.00248

GnomAD4 exome

AF:

0.00240

AC:

3494

AN:

1452906

Hom.:

Cov.:

AF XY:

0.00211

AC XY:

1524

AN XY:

723584

show subpopulations

African (AFR)

AF:

0.0783

AC:

2601

AN:

33236

American (AMR)

AF:

0.00467

AC:

209

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.000422

AC:

AN:

26062

East Asian (EAS)

AF:

0.000101

AC:

AN:

39646

South Asian (SAS)

AF:

0.000314

AC:

AN:

86090

European-Finnish (FIN)

AF:

0.000131

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00729

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000251

AC:

277

AN:

1103876

Other (OTH)

AF:

0.00526

AC:

316

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

167

333

500

666

833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

180

270

360

450

<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:

0.0219

AC:

3338

AN:

152306

Hom.:

146

Cov.:

AF XY:

0.0217

AC XY:

1616

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.0761

AC:

3163

AN:

41548

American (AMR)

AF:

0.00778

AC:

119

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000621

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000309

AC:

AN:

68028

Other (OTH)

AF:

0.0142

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

153

307

460

614

767

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00785

Hom.:

136

Bravo

AF:

0.0244

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 25, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.12

(source)

DANN

Benign

0.15

PhyloP100

-1.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over