13-20404888-G-A

Position:

• chr13-20404888-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.740-147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.738 in 627,394 control chromosomes in the GnomAD database, including 171,667 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.73 (40848 hom., cov: 32)
  • Exomes 𝑓: 0.74 (130819 hom.)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.143

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=-0.9).
• BP6: Variant 13-20404888-G-A is Benign according to our data. Variant chr13-20404888-G-A is described in ClinVar as [Benign]. Clinvar id is 1248552.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.740-147C>T		intron_variant		ENST00000298248.12
CRYL1	NM_001363647.2	c.578-147C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYL1	ENST00000298248.12	c.740-147C>T		intron_variant		1	NM_015974.3	P1

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111074 AN: 151558 Hom.: 40825 Cov.: 32

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.737

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.762

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.741

GnomAD4 exome AF: 0.739 AC: 351725 AN: 475718 Hom.: 130819 AF XY: 0.742 AC XY: 188388 AN XY: 253884

Gnomad4 AFR exome AF: 0.705

Gnomad4 AMR exome AF: 0.726

Gnomad4 ASJ exome AF: 0.766

Gnomad4 EAS exome AF: 0.632

Gnomad4 SAS exome AF: 0.769

Gnomad4 FIN exome AF: 0.687

Gnomad4 NFE exome AF: 0.753

Gnomad4 OTH exome AF: 0.740

GnomAD4 genome AF: 0.733 AC: 111147 AN: 151676 Hom.: 40848 Cov.: 32 AF XY: 0.730 AC XY: 54099 AN XY: 74112

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.762

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.735

Alfa AF: 0.741 Hom.: 5434

Bravo AF: 0.735

Asia WGS AF: 0.662 AC: 2299 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	-0.90
CADD	Benign	2.3
DANN	Benign	0.69

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: rs7331073; hg19: chr13-20979027;