13-20404525-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015974.3(CRYL1):c.846+110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 725,922 control chromosomes in the GnomAD database, including 206,826 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (42487 hom., cov: 29)
  • Exomes 𝑓: 0.76 (164339 hom.)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.484

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 13-20404525-T-C is Benign according to our data. Variant chr13-20404525-T-C is described in ClinVar as [Benign]. Clinvar id is 1286617.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYL1	NM_015974.3	c.846+110A>G		intron_variant		ENST00000298248.12
CRYL1	NM_001363647.2	c.684+110A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYL1	ENST00000298248.12	c.846+110A>G		intron_variant		1	NM_015974.3	P1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113267 AN: 151542 Hom.: 42463 Cov.: 29

Gnomad AFR AF: 0.715

Gnomad AMI AF: 0.778

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.756

Gnomad OTH AF: 0.754

GnomAD4 exome AF: 0.756 AC: 434058 AN: 574262 Hom.: 164339 AF XY: 0.757 AC XY: 231917 AN XY: 306220

Gnomad4 AFR exome AF: 0.715

Gnomad4 AMR exome AF: 0.874

Gnomad4 ASJ exome AF: 0.769

Gnomad4 EAS exome AF: 0.713

Gnomad4 SAS exome AF: 0.776

Gnomad4 FIN exome AF: 0.693

Gnomad4 NFE exome AF: 0.758

Gnomad4 OTH exome AF: 0.752

GnomAD4 genome AF: 0.747 AC: 113343 AN: 151660 Hom.: 42487 Cov.: 29 AF XY: 0.746 AC XY: 55302 AN XY: 74108

Gnomad4 AFR AF: 0.715

Gnomad4 AMR AF: 0.831

Gnomad4 ASJ AF: 0.767

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.707

Gnomad4 NFE AF: 0.756

Gnomad4 OTH AF: 0.749

Alfa AF: 0.757 Hom.: 74041

Bravo AF: 0.755

Asia WGS AF: 0.692 AC: 2404 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	2.9
Dann	Benign	0.28
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3737036; hg19: chr13-20978664; COSMIC: COSV53420240;