Variant 12-91056207-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KERA	NM_007035.4 linkuse as main transcript	c.75G>A	p.Gln25Gln	synonymous_variant	2/3	ENST00000266719.4	NP_008966.1	O60938

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KERA	ENST00000266719.4 linkuse as main transcript	c.75G>A	p.Gln25Gln	synonymous_variant	2/3	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

GnomAD3 exomes

AF:

0.142

AC:

35189

AN:

248506

Hom.:

3807

AF XY:

0.132

AC XY:

17720

AN XY:

134340

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 SAS exome

AF:

0.0636

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

Gnomad4 AFR exome

AF:

0.502

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.197

Gnomad4 EAS exome

AF:

0.0861

Gnomad4 SAS exome

AF:

0.0641

Gnomad4 FIN exome

AF:

0.0823

Gnomad4 NFE exome

AF:

0.125

Gnomad4 OTH exome

AF:

0.142

GnomAD4 genome

AF:

0.227

AC:

34226

AN:

150952

Hom.:

6021

Cov.:

AF XY:

0.218

AC XY:

16097

AN XY:

73744

show subpopulations

Gnomad4 AFR

AF:

0.493

Gnomad4 AMR

AF:

0.160

Gnomad4 ASJ

AF:

0.193

Gnomad4 EAS

AF:

0.0736

Gnomad4 SAS

AF:

0.0562

Gnomad4 FIN

AF:

0.0815

Gnomad4 NFE

AF:

0.130

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.151

Hom.:

1524

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

7.5

DANN

Benign

0.66

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

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