13-20413589-A-G

Position:

• chr13-20413589-A-G

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.634-202T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,160 control chromosomes in the GnomAD database, including 42,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.74 (42398 hom., cov: 33)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.494

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=-0.98).
• BP6: Variant 13-20413589-A-G is Benign according to our data. Variant chr13-20413589-A-G is described in ClinVar as [Benign]. Clinvar id is 1233024.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYL1	NM_015974.3	c.634-202T>C		intron_variant		ENST00000298248.12
CRYL1	NM_001363647.2	c.472-202T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYL1	ENST00000298248.12	c.634-202T>C		intron_variant		1	NM_015974.3	P1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113234 AN: 152042 Hom.: 42377 Cov.: 33

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.827

Gnomad ASJ AF: 0.772

Gnomad EAS AF: 0.694

Gnomad SAS AF: 0.766

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.752

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

GnomAD4 genome AF: 0.745 AC: 113305 AN: 152160 Hom.: 42398 Cov.: 33 AF XY: 0.744 AC XY: 55332 AN XY: 74388

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.827

Gnomad4 ASJ AF: 0.772

Gnomad4 EAS AF: 0.694

Gnomad4 SAS AF: 0.766

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.757

Gnomad4 OTH AF: 0.747

Alfa AF: 0.749 Hom.: 5288

Bravo AF: 0.751

Asia WGS AF: 0.686 AC: 2383 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	-0.98
CADD	Benign	0.28
DANN	Benign	0.34

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: rs9509206; hg19: chr13-20987728;