12-91052319-T-A

Variant names:

• chr12-91052319-T-A
• rs1920773
• NM_007035.4:c.887-801A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007035.4(KERA):​c.887-801A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 151,316 control chromosomes in the GnomAD database, including 57,882 homozygotes. 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: 𝑓 0.87 (57882 hom., cov: 30)
• Consequence: KERA NM_007035.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KERA	NM_007035.4	c.887-801A>T		intron_variant	Intron 2 of 2	ENST00000266719.4	NP_008966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KERA	ENST00000266719.4	c.887-801A>T		intron_variant	Intron 2 of 2	1	NM_007035.4	ENSP00000266719.3

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132162 AN: 151198 Hom.: 57840 Cov.: 30

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.906

Gnomad ASJ AF: 0.843

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.947

Gnomad FIN AF: 0.933

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.874

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.874 AC: 132255 AN: 151316 Hom.: 57882 Cov.: 30 AF XY: 0.878 AC XY: 64919 AN XY: 73942

African (AFR) AF: 0.815 AC: 33671 AN: 41332

American (AMR) AF: 0.906 AC: 13722 AN: 15148

Ashkenazi Jewish (ASJ) AF: 0.843 AC: 2905 AN: 3446

East Asian (EAS) AF: 0.929 AC: 4741 AN: 5104

South Asian (SAS) AF: 0.947 AC: 4558 AN: 4812

European-Finnish (FIN) AF: 0.933 AC: 9899 AN: 10612

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 59978 AN: 67560

Other (OTH) AF: 0.871 AC: 1828 AN: 2098

Alfa AF: 0.879 Hom.: 7302

Bravo AF: 0.869

Asia WGS AF: 0.938 AC: 3257 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.5
DANN	Benign	0.63
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1920773; hg19: chr12-91446096;