13-20519465-C-T

Position:

• chr13-20519465-C-T

Variant summary

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

The ENST00000298248.12(CRYL1):​c.41+6289G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.845 in 152,070 control chromosomes in the GnomAD database, including 57,207 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 0.84 (57207 hom., cov: 31)
• Consequence: CRYL1 ENST00000298248.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.135

Genes affected

CRYL1 (HGNC:18246): (crystallin lambda 1) The uronate cycle functions as an alternative glucose metabolic pathway, accounting for about 5% of daily glucose catabolism. The product of this gene catalyzes the dehydrogenation of L-gulonate into dehydro-L-gulonate in the uronate cycle. The enzyme requires NAD(H) as a coenzyme, and is inhibited by inorganic phosphate. A similar gene in the rabbit is thought to serve a structural role in the lens of the eye. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYL1	NM_015974.3	c.41+6289G>A		intron_variant		ENST00000298248.12	NP_057058.2
CRYL1	NM_001363647.2	c.41+6289G>A		intron_variant			NP_001350576.1
CRYL1	XM_005266416.6	c.41+6289G>A		intron_variant			XP_005266473.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYL1	ENST00000298248.12	c.41+6289G>A		intron_variant		1	NM_015974.3	ENSP00000298248	P1

Frequencies

GnomAD3 genomes AF: 0.845 AC: 128412 AN: 151952 Hom.: 57184 Cov.: 31

Gnomad AFR AF: 0.529

Gnomad AMI AF: 0.916

Gnomad AMR AF: 0.915

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.966

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.972

Gnomad OTH AF: 0.867

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

GnomAD4 genome AF: 0.845 AC: 128472 AN: 152070 Hom.: 57207 Cov.: 31 AF XY: 0.851 AC XY: 63231 AN XY: 74338

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.915

Gnomad4 ASJ AF: 0.910

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.967

Gnomad4 FIN AF: 0.996

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.868

Alfa AF: 0.924 Hom.: 26279

Bravo AF: 0.824

Asia WGS AF: 0.965 AC: 3356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.70

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: rs4770049; hg19: chr13-21093604;