rs11105957

chr12-91056876-A-Gchr12-91056876-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007035.4(KERA):c.-8-587T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 150,856 control chromosomes in the GnomAD database, including 10,560 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 (10560 hom., cov: 31)
• Consequence: KERA NM_007035.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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=-0.59).
• 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/exons	MANE	UniProt
KERA	NM_007035.4	c.-8-587T>C		intron_variant		ENST00000266719.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KERA	ENST00000266719.4	c.-8-587T>C		intron_variant		1	NM_007035.4	P1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 47970 AN: 150738 Hom.: 10528 Cov.: 31

Gnomad AFR AF: 0.630

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.319 AC: 48055 AN: 150856 Hom.: 10560 Cov.: 31 AF XY: 0.314 AC XY: 23139 AN XY: 73708

Gnomad4 AFR AF: 0.630

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.253

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.274

Alfa AF: 0.138 Hom.: 267

Bravo AF: 0.345

Asia WGS AF: 0.264 AC: 920 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	12
Dann	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs11105957; hg19: chr12-91450653;