12-91058164-T-G

Variant names:

• chr12-91058164-T-G
• rs1990548
• NM_007035.4:c.-429A>C

Variant summary

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

The NM_007035.4(KERA):​c.-429A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 150,992 control chromosomes in the GnomAD database, including 10,546 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 0.32 (10546 hom., cov: 32)
• Consequence: KERA NM_007035.4 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.623 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007035.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KERA	NM_007035.4	MANE Select	c.-429A>C		upstream_gene	N/A	NP_008966.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KERA	ENST00000266719.4	TSL:1 MANE Select	c.-429A>C		upstream_gene	N/A	ENSP00000266719.3

Frequencies

GnomAD3 genomes AF: 0.318 AC: 47975 AN: 150874 Hom.: 10514 Cov.: 32

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.318 AC: 48060 AN: 150992 Hom.: 10546 Cov.: 32 AF XY: 0.314 AC XY: 23140 AN XY: 73760

African (AFR) AF: 0.630 AC: 25972 AN: 41256

American (AMR) AF: 0.279 AC: 4210 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.239 AC: 822 AN: 3444

East Asian (EAS) AF: 0.203 AC: 1041 AN: 5122

South Asian (SAS) AF: 0.253 AC: 1215 AN: 4810

European-Finnish (FIN) AF: 0.157 AC: 1661 AN: 10562

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12356 AN: 67408

Other (OTH) AF: 0.275 AC: 573 AN: 2084

Alfa AF: 0.227 Hom.: 13109

Bravo AF: 0.345

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.37
PhyloP100		-0.013
PromoterAI		0.0024	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1990548; hg19: chr12-91451941;