12-91058164-T-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KERA	NM_007035.4	c.-429A>C		upstream_gene_variant		ENST00000266719.4	NP_008966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KERA	ENST00000266719.4	c.-429A>C		upstream_gene_variant		1	NM_007035.4	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

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.203

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.183

Gnomad4 OTH AF: 0.275

Alfa AF: 0.196 Hom.: 5389

Bravo AF: 0.345

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1990548; hg19: chr12-91451941;