13-20404965-G-A

Position:

• chr13-20404965-G-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.740-224C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,954 control chromosomes in the GnomAD database, including 42,483 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.75 (42483 hom., cov: 31)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.429

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=-0.94).
• BP6: Variant 13-20404965-G-A is Benign according to our data. Variant chr13-20404965-G-A is described in ClinVar as [Benign]. Clinvar id is 1233052.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.740-224C>T		intron_variant		ENST00000298248.12	NP_057058.2
CRYL1	NM_001363647.2	c.578-224C>T		intron_variant			NP_001350576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYL1	ENST00000298248.12	c.740-224C>T		intron_variant		1	NM_015974.3	ENSP00000298248.7

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113286 AN: 151834 Hom.: 42460 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.705

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.755

Gnomad OTH AF: 0.753

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

GnomAD4 genome AF: 0.746 AC: 113361 AN: 151954 Hom.: 42483 Cov.: 31 AF XY: 0.745 AC XY: 55294 AN XY: 74220

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.830

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.696

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.705

Gnomad4 NFE AF: 0.755

Gnomad4 OTH AF: 0.748

Alfa AF: 0.765 Hom.: 7547

Bravo AF: 0.755

Asia WGS AF: 0.689 AC: 2394 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	-0.94
CADD	Benign	0.77
DANN	Benign	0.51

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: rs6490564; hg19: chr13-20979104;