13-20404889-C-A

Position:

• chr13-20404889-C-A

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.740-148G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 622,672 control chromosomes in the GnomAD database, including 176,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (42396 hom., cov: 31)
  • Exomes 𝑓: 0.75 (134224 hom.)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.266

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]

CRYL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 13-20404889-C-A is Benign according to our data. Variant chr13-20404889-C-A is described in ClinVar as [Benign]. Clinvar id is 1239329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYL1	NM_015974.3	c.740-148G>T		intron_variant		ENST00000298248.12	NP_057058.2
CRYL1	NM_001363647.2	c.578-148G>T		intron_variant			NP_001350576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYL1	ENST00000298248.12	c.740-148G>T		intron_variant		1	NM_015974.3	ENSP00000298248.7

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113099 AN: 151564 Hom.: 42372 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.753

GnomAD4 exome AF: 0.753 AC: 354502 AN: 470990 Hom.: 134224 AF XY: 0.754 AC XY: 189387 AN XY: 251178

Gnomad4 AFR exome AF: 0.712

Gnomad4 AMR exome AF: 0.864

Gnomad4 ASJ exome AF: 0.768

Gnomad4 EAS exome AF: 0.709

Gnomad4 SAS exome AF: 0.773

Gnomad4 FIN exome AF: 0.690

Gnomad4 NFE exome AF: 0.754

Gnomad4 OTH exome AF: 0.752

GnomAD4 genome AF: 0.746 AC: 113175 AN: 151682 Hom.: 42396 Cov.: 31 AF XY: 0.745 AC XY: 55203 AN XY: 74108

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.748

Alfa AF: 0.750 Hom.: 5311

Bravo AF: 0.756

Asia WGS AF: 0.692 AC: 2405 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	-1.0
CADD	Benign	0.62
DANN	Benign	0.72

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: rs3818618; hg19: chr13-20979028;