13-20404365-C-T

Position:

• chr13-20404365-C-T

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.847-123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 666,336 control chromosomes in the GnomAD database, including 177,639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.70 (37523 hom., cov: 32)
  • Exomes 𝑓: 0.74 (140116 hom.)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.298

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 13-20404365-C-T is Benign according to our data. Variant chr13-20404365-C-T is described in ClinVar as [Benign]. Clinvar id is 1244887.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYL1	NM_015974.3	c.847-123G>A		intron_variant		ENST00000298248.12
CRYL1	NM_001363647.2	c.685-123G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYL1	ENST00000298248.12	c.847-123G>A		intron_variant		1	NM_015974.3	P1

Frequencies

GnomAD3 genomes AF: 0.698 AC: 106116 AN: 151998 Hom.: 37509 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.777

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.723

GnomAD4 exome AF: 0.736 AC: 378483 AN: 514220 Hom.: 140116 AF XY: 0.740 AC XY: 200981 AN XY: 271658

Gnomad4 AFR exome AF: 0.584

Gnomad4 AMR exome AF: 0.718

Gnomad4 ASJ exome AF: 0.764

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.769

Gnomad4 FIN exome AF: 0.689

Gnomad4 NFE exome AF: 0.753

Gnomad4 OTH exome AF: 0.730

GnomAD4 genome AF: 0.698 AC: 106169 AN: 152116 Hom.: 37523 Cov.: 32 AF XY: 0.696 AC XY: 51716 AN XY: 74346

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.722

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.704

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.717

Alfa AF: 0.725 Hom.: 6808

Bravo AF: 0.694

Asia WGS AF: 0.651 AC: 2262 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	-0.89
CADD	Benign	12
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs4638418; hg19: chr13-20978504;