Variant chr12-91056213-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.69G>A(p.Val23Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 1,609,058 control chromosomes in the GnomAD database, including 471,924 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 35010 hom., cov: 31)

Exomes 𝑓: 0.77 ( 436914 hom. )

Consequence

KERA
NM_007035.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.08

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=-0.47).

BP6

Variant 12-91056213-C-T is Benign according to our data. Variant chr12-91056213-C-T is described in ClinVar as [Benign]. Clinvar id is 1174695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-91056213-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.09 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.777 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.69G>A	p.Val23Val	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.69G>A	p.Val23Val	synonymous_variant	2/3	1	NM_007035.4	ENSP00000266719.3		O60938

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

98401

AN:

150820

Hom.:

35004

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.680

Gnomad AMR

AF:

0.700

Gnomad ASJ

AF:

0.749

Gnomad EAS

AF:

0.797

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.826

Gnomad MID

AF:

0.699

Gnomad NFE

AF:

0.782

Gnomad OTH

AF:

0.696

GnomAD3 exomes

AF:

0.732

AC:

181842

AN:

248542

Hom.:

68413

AF XY:

0.743

AC XY:

99817

AN XY:

134362

show subpopulations

Gnomad AFR exome

AF:

0.319

Gnomad AMR exome

AF:

0.656

Gnomad ASJ exome

AF:

0.745

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.738

Gnomad FIN exome

AF:

0.828

Gnomad NFE exome

AF:

0.782

Gnomad OTH exome

AF:

0.761

GnomAD4 exome

AF:

0.770

AC:

1123059

AN:

1458120

Hom.:

436914

Cov.:

AF XY:

0.771

AC XY:

559110

AN XY:

725406

show subpopulations

Gnomad4 AFR exome

AF:

0.327

Gnomad4 AMR exome

AF:

0.661

Gnomad4 ASJ exome

AF:

0.752

Gnomad4 EAS exome

AF:

0.781

Gnomad4 SAS exome

AF:

0.741

Gnomad4 FIN exome

AF:

0.824

Gnomad4 NFE exome

AF:

0.788

Gnomad4 OTH exome

AF:

0.758

GnomAD4 genome

AF:

0.652

AC:

98428

AN:

150938

Hom.:

35010

Cov.:

AF XY:

0.657

AC XY:

48486

AN XY:

73760

show subpopulations

Gnomad4 AFR

AF:

0.339

Gnomad4 AMR

AF:

0.700

Gnomad4 ASJ

AF:

0.749

Gnomad4 EAS

AF:

0.797

Gnomad4 SAS

AF:

0.738

Gnomad4 FIN

AF:

0.826

Gnomad4 NFE

AF:

0.782

Gnomad4 OTH

AF:

0.694

Alfa

AF:

0.762

Hom.:

64334

Bravo

AF:

0.626

Asia WGS

AF:

0.728

AC:

2531

AN:

3478

EpiCase

AF:

0.789

EpiControl

AF:

0.778

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

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	-	- -

Cornea plana 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.7

DANN

Benign

0.62

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

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