chr12-91051468-G-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_007035.4(KERA):​c.937C>A​(p.Arg313Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

KERA
NM_007035.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.40

Publications

6 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP7
Synonymous conserved (PhyloP=2.39 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KERANM_007035.4 linkc.937C>A p.Arg313Arg synonymous_variant Exon 3 of 3 ENST00000266719.4 NP_008966.1 O60938

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KERAENST00000266719.4 linkc.937C>A p.Arg313Arg synonymous_variant Exon 3 of 3 1 NM_007035.4 ENSP00000266719.3 O60938

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000399
AC:
1
AN:
250408
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1458984
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
725878
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33328
American (AMR)
AF:
0.00
AC:
0
AN:
44544
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26030
East Asian (EAS)
AF:
0.0000252
AC:
1
AN:
39658
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86198
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53340
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5752
European-Non Finnish (NFE)
AF:
9.01e-7
AC:
1
AN:
1109930
Other (OTH)
AF:
0.00
AC:
0
AN:
60204
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000434
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
4.7
DANN
Benign
0.40
PhyloP100
2.4

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

Other links and lift over

dbSNP: rs121917863; hg19: chr12-91445245; API