13-20404819-CAG-C

Position:

• chr13-20404819-CAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015974.3(CRYL1):​c.740-80_740-79delCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0973 in 969,474 control chromosomes in the GnomAD database, including 6,134 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.087 (835 hom., cov: 30)
  • Exomes 𝑓: 0.099 (5299 hom.)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.836

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 -10 ACMG points.

• BP6: Variant 13-20404819-CAG-C is Benign according to our data. Variant chr13-20404819-CAG-C is described in ClinVar as [Benign]. Clinvar id is 1276123.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYL1	NM_015974.3	c.740-80_740-79delCT		intron_variant		ENST00000298248.12	NP_057058.2
CRYL1	NM_001363647.2	c.578-80_578-79delCT		intron_variant			NP_001350576.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYL1	ENST00000298248.12	c.740-80_740-79delCT		intron_variant		1	NM_015974.3	ENSP00000298248.7

Frequencies

GnomAD3 genomes AF: 0.0873 AC: 13274 AN: 152136 Hom.: 832 Cov.: 30

Gnomad AFR AF: 0.0221

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0689

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0771

GnomAD4 exome AF: 0.0992 AC: 81035 AN: 817220 Hom.: 5299 AF XY: 0.0961 AC XY: 41223 AN XY: 429032

Gnomad4 AFR exome AF: 0.0163

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.0653

Gnomad4 EAS exome AF: 0.000355

Gnomad4 SAS exome AF: 0.0398

Gnomad4 FIN exome AF: 0.148

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.0913

GnomAD4 genome AF: 0.0872 AC: 13279 AN: 152254 Hom.: 835 Cov.: 30 AF XY: 0.0876 AC XY: 6521 AN XY: 74438

Gnomad4 AFR AF: 0.0221

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0689

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0355

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0763

Alfa AF: 0.109 Hom.: 134

Bravo AF: 0.0871

Asia WGS AF: 0.0270 AC: 94 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

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: rs67871298; hg19: chr13-20978958;