Genetic Variant KERA:p.Gln25Gln (chr12-91056207-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_007035.4(KERA):c.75G>A(p.Gln25Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,608,832 control chromosomes in the GnomAD database, including 21,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 6021 hom., cov: 32)

Exomes 𝑓: 0.13 ( 15241 hom. )

Consequence

KERA
NM_007035.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.63

Publications

13 publications found

Variant links:

Genes affected

KERA (HGNC:6309): (keratocan) The protein encoded by this gene is a keratan sulfate proteoglycan that is involved in corneal transparency. Defects in this gene are a cause of autosomal recessive cornea plana 2 (CNA2).[provided by RefSeq, May 2010]

KERA Gene-Disease associations (from GenCC):

cornea plana
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
cornea plana 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
congenital cornea plana
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KERA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 12-91056207-C-T is Benign according to our data. Variant chr12-91056207-C-T is described in ClinVar as [Benign]. Clinvar id is 1547721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.63 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KERA	NM_007035.4 link	c.75G>A	p.Gln25Gln	synonymous_variant	Exon 2 of 3	ENST00000266719.4	NP_008966.1	O60938

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KERA	ENST00000266719.4 link	c.75G>A	p.Gln25Gln	synonymous_variant	Exon 2 of 3	1	NM_007035.4	ENSP00000266719.3		O60938

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34159

AN:

150834

Hom.:

5999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.493

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.160

Gnomad ASJ

AF:

0.193

Gnomad EAS

AF:

0.0737

Gnomad SAS

AF:

0.0562

Gnomad FIN

AF:

0.0815

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.201

GnomAD2 exomes

AF:

0.142

AC:

35189

AN:

248506

AF XY:

0.132

show subpopulations

Gnomad AFR exome

AF:

0.509

Gnomad AMR exome

AF:

0.134

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.0807

Gnomad FIN exome

AF:

0.0785

Gnomad NFE exome

AF:

0.129

Gnomad OTH exome

AF:

0.138

GnomAD4 exome

AF:

0.130

AC:

189385

AN:

1457880

Hom.:

15241

Cov.:

AF XY:

0.127

AC XY:

92218

AN XY:

725336

show subpopulations

African (AFR)

AF:

0.502

AC:

16694

AN:

33274

American (AMR)

AF:

0.138

AC:

6149

AN:

44532

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

5119

AN:

25992

East Asian (EAS)

AF:

0.0861

AC:

3409

AN:

39616

South Asian (SAS)

AF:

0.0641

AC:

5519

AN:

86114

European-Finnish (FIN)

AF:

0.0823

AC:

4377

AN:

53162

Middle Eastern (MID)

AF:

0.177

AC:

1017

AN:

5738

European-Non Finnish (NFE)

AF:

0.125

AC:

138575

AN:

1109272

Other (OTH)

AF:

0.142

AC:

8526

AN:

60180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

8911

17822

26734

35645

44556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5084

10168

15252

20336

25420

<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:

0.227

AC:

34226

AN:

150952

Hom.:

6021

Cov.:

AF XY:

0.218

AC XY:

16097

AN XY:

73744

show subpopulations

African (AFR)

AF:

0.493

AC:

20376

AN:

41302

American (AMR)

AF:

0.160

AC:

2409

AN:

15096

Ashkenazi Jewish (ASJ)

AF:

0.193

AC:

666

AN:

3444

East Asian (EAS)

AF:

0.0736

AC:

376

AN:

5106

South Asian (SAS)

AF:

0.0562

AC:

271

AN:

4818

European-Finnish (FIN)

AF:

0.0815

AC:

863

AN:

10586

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.130

AC:

8727

AN:

67294

Other (OTH)

AF:

0.203

AC:

426

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1141

2282

3423

4564

5705

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<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:

0.142

Hom.:

4284

Bravo

AF:

0.246

Asia WGS

AF:

0.0890

AC:

311

AN:

3478

EpiCase

AF:

0.133

EpiControl

AF:

0.133

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.5

(source)

DANN

Benign

0.66

PhyloP100

2.6

Mutation Taster

=89/11

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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