13-20404476-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.846+159C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,006 control chromosomes in the GnomAD database, including 3,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3511 hom., cov: 31)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.961

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=-0.89).
• BP6: Variant 13-20404476-G-A is Benign according to our data. Variant chr13-20404476-G-A is described in ClinVar as [Benign]. Clinvar id is 1257693.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYL1	NM_015974.3	c.846+159C>T		intron_variant		ENST00000298248.12
CRYL1	NM_001363647.2	c.684+159C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYL1	ENST00000298248.12	c.846+159C>T		intron_variant		1	NM_015974.3	P1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30718 AN: 151888 Hom.: 3509 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.208

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

GnomAD4 genome AF: 0.202 AC: 30726 AN: 152006 Hom.: 3511 Cov.: 31 AF XY: 0.204 AC XY: 15158 AN XY: 74288

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.213

Alfa AF: 0.145 Hom.: 357

Bravo AF: 0.185

Asia WGS AF: 0.296 AC: 1032 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.77
Dann	Benign	0.50

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: rs3737037; hg19: chr13-20978615; COSMIC: COSV53422837;