chr13-20404889-C-A

Variant names:

• chr13-20404889-C-A
• rs3818618
• NM_015974.3:c.740-148G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015974.3(CRYL1):​c.740-148G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.751 in 622,672 control chromosomes in the GnomAD database, including 176,620 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.75 (42396 hom., cov: 31)
  • Exomes 𝑓: 0.75 (134224 hom.)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.266
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 13-20404889-C-A is Benign according to our data. Variant chr13-20404889-C-A is described in ClinVar as Benign. ClinVar VariationId is 1239329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015974.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYL1	NM_015974.3	MANE Select	c.740-148G>T		intron	N/A	NP_057058.2	Q9Y2S2-1
	CRYL1	NM_001363647.2		c.578-148G>T		intron	N/A	NP_001350576.1	A0A2R8Y4K2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYL1	ENST00000298248.12	TSL:1 MANE Select	c.740-148G>T		intron	N/A	ENSP00000298248.7	Q9Y2S2-1
	CRYL1	ENST00000382812.5	TSL:1	c.674-148G>T		intron	N/A	ENSP00000372262.1	Q9Y2S2-2
	CRYL1	ENST00000887623.1		c.701-148G>T		intron	N/A	ENSP00000557682.1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113099 AN: 151564 Hom.: 42372 Cov.: 31

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.775

Gnomad AMR AF: 0.830

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.704

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.753

GnomAD4 exome AF: 0.753 AC: 354502 AN: 470990 Hom.: 134224 AF XY: 0.754 AC XY: 189387 AN XY: 251178

African (AFR) AF: 0.712 AC: 9481 AN: 13316

American (AMR) AF: 0.864 AC: 18592 AN: 21508

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 10589 AN: 13780

East Asian (EAS) AF: 0.709 AC: 22230 AN: 31360

South Asian (SAS) AF: 0.773 AC: 37787 AN: 48866

European-Finnish (FIN) AF: 0.690 AC: 21605 AN: 31334

Middle Eastern (MID) AF: 0.757 AC: 1481 AN: 1956

European-Non Finnish (NFE) AF: 0.754 AC: 212986 AN: 282606

Other (OTH) AF: 0.752 AC: 19751 AN: 26264

GnomAD4 genome AF: 0.746 AC: 113175 AN: 151682 Hom.: 42396 Cov.: 31 AF XY: 0.745 AC XY: 55203 AN XY: 74108

African (AFR) AF: 0.714 AC: 29561 AN: 41384

American (AMR) AF: 0.830 AC: 12669 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2647 AN: 3462

East Asian (EAS) AF: 0.696 AC: 3581 AN: 5144

South Asian (SAS) AF: 0.767 AC: 3688 AN: 4810

European-Finnish (FIN) AF: 0.704 AC: 7383 AN: 10488

Middle Eastern (MID) AF: 0.702 AC: 205 AN: 292

European-Non Finnish (NFE) AF: 0.754 AC: 51167 AN: 67836

Other (OTH) AF: 0.748 AC: 1573 AN: 2104

Alfa AF: 0.750 Hom.: 5311

Bravo AF: 0.756

Asia WGS AF: 0.692 AC: 2405 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.62
DANN	Benign	0.72
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3818618; hg19: chr13-20979028;