Variant 12-91051526-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_007035.4(KERA):c.887-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 1,589,822 control chromosomes in the GnomAD database, including 46,607 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.18 ( 3137 hom., cov: 32)

Exomes 𝑓: 0.24 ( 43470 hom. )

Consequence

KERA
NM_007035.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00001873

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.235

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-91051526-G-A is Benign according to our data. Variant chr12-91051526-G-A is described in ClinVar as [Benign]. Clinvar id is 1530150.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-91051526-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KERA	NM_007035.4 linkuse as main transcript	c.887-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000266719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KERA	ENST00000266719.4 linkuse as main transcript	c.887-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_007035.4	P1

Frequencies

GnomAD3 genomes

AF:

0.183

AC:

27644

AN:

151432

Hom.:

3137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0673

Gnomad AMI

AF:

0.183

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.0113

Gnomad SAS

AF:

0.135

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.209

Gnomad NFE

AF:

0.254

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.194

AC:

48409

AN:

249190

Hom.:

5585

AF XY:

0.197

AC XY:

26556

AN XY:

134664

show subpopulations

Gnomad AFR exome

AF:

0.0592

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.208

Gnomad EAS exome

AF:

0.00994

Gnomad SAS exome

AF:

0.146

Gnomad FIN exome

AF:

0.288

Gnomad NFE exome

AF:

0.250

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.236

AC:

339190

AN:

1438272

Hom.:

43470

Cov.:

AF XY:

0.234

AC XY:

167852

AN XY:

716714

show subpopulations

Gnomad4 AFR exome

AF:

0.0567

Gnomad4 AMR exome

AF:

0.154

Gnomad4 ASJ exome

AF:

0.210

Gnomad4 EAS exome

AF:

0.00536

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.284

Gnomad4 NFE exome

AF:

0.260

Gnomad4 OTH exome

AF:

0.216

GnomAD4 genome

AF:

0.182

AC:

27639

AN:

151550

Hom.:

3137

Cov.:

AF XY:

0.180

AC XY:

13318

AN XY:

74028

show subpopulations

Gnomad4 AFR

AF:

0.0670

Gnomad4 AMR

AF:

0.172

Gnomad4 ASJ

AF:

0.208

Gnomad4 EAS

AF:

0.0115

Gnomad4 SAS

AF:

0.135

Gnomad4 FIN

AF:

0.289

Gnomad4 NFE

AF:

0.254

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.233

Hom.:

4820

Bravo

AF:

0.168

Asia WGS

AF:

0.0720

AC:

250

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.5

DANN

Benign

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000019

dbscSNV1_RF

Benign

0.0020

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