rs7989332

chr13-20476436-A-Cchr13-20476436-A-Gchr13-20476436-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015974.3(CRYL1):c.276+12934T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 151,866 control chromosomes in the GnomAD database, including 43,306 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.75 (43306 hom., cov: 30)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.807 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYL1	NM_015974.3	c.276+12934T>G		intron_variant		ENST00000298248.12
CRYL1	NM_001363647.2	c.276+12934T>G		intron_variant
CRYL1	XM_005266416.6	c.276+12934T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYL1	ENST00000298248.12	c.276+12934T>G		intron_variant		1	NM_015974.3	P1

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114262 AN: 151752 Hom.: 43263 Cov.: 30

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.796

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.798

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.716

Gnomad OTH AF: 0.766

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

GnomAD4 genome AF: 0.753 AC: 114357 AN: 151866 Hom.: 43306 Cov.: 30 AF XY: 0.753 AC XY: 55874 AN XY: 74218

Gnomad4 AFR AF: 0.815

Gnomad4 AMR AF: 0.797

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.798

Gnomad4 SAS AF: 0.774

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.761

Alfa AF: 0.726 Hom.: 47144

Bravo AF: 0.765

Asia WGS AF: 0.786 AC: 2731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	3.8
Dann	Benign	0.40

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: rs7989332; hg19: chr13-21050575;