12-91053746-A-G

Position:

• chr12-91053746-A-G

Variant summary

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

The NM_007035.4(KERA):​c.886+1650T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 151,372 control chromosomes in the GnomAD database, including 709 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 0.087 (709 hom., cov: 32)
• Consequence: KERA NM_007035.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KERA	NM_007035.4	c.886+1650T>C		intron_variant		ENST00000266719.4	NP_008966.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KERA	ENST00000266719.4	c.886+1650T>C		intron_variant		1	NM_007035.4	ENSP00000266719	P1

Frequencies

GnomAD3 genomes AF: 0.0866 AC: 13093 AN: 151254 Hom.: 709 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0755

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0537

Gnomad OTH AF: 0.0708

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

GnomAD4 genome AF: 0.0866 AC: 13107 AN: 151372 Hom.: 709 Cov.: 32 AF XY: 0.0908 AC XY: 6713 AN XY: 73942

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.199

Gnomad4 FIN AF: 0.0755

Gnomad4 NFE AF: 0.0537

Gnomad4 OTH AF: 0.0701

Alfa AF: 0.0717 Hom.: 58

Bravo AF: 0.0917

Asia WGS AF: 0.176 AC: 612 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.77
DANN	Benign	0.39

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: rs11105956; hg19: chr12-91447523;