rs4638418

Variant names:

• chr13-20404365-C-T
• rs4638418
• NM_015974.3:c.847-123G>A

Your query was ambiguous. Multiple possible variants found:

• chr13-20404365-C-T
• chr13-20404365-C-A
• chr13-20404365-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.298
• Publications: 5 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 -20 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 VariationId is 1244887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.748 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.847-123G>A		intron	N/A	NP_057058.2	Q9Y2S2-1
	CRYL1	NM_001363647.2		c.685-123G>A		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.847-123G>A		intron	N/A	ENSP00000298248.7	Q9Y2S2-1
	CRYL1	ENST00000382812.5	TSL:1	c.781-123G>A		intron	N/A	ENSP00000372262.1	Q9Y2S2-2
	CRYL1	ENST00000887623.1		c.808-123G>A		intron	N/A	ENSP00000557682.1

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

African (AFR) AF: 0.584 AC: 8148 AN: 13962

American (AMR) AF: 0.718 AC: 16791 AN: 23388

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 11640 AN: 15228

East Asian (EAS) AF: 0.632 AC: 20036 AN: 31678

South Asian (SAS) AF: 0.769 AC: 37840 AN: 49186

European-Finnish (FIN) AF: 0.689 AC: 21788 AN: 31612

Middle Eastern (MID) AF: 0.745 AC: 1912 AN: 2566

European-Non Finnish (NFE) AF: 0.753 AC: 239462 AN: 318022

Other (OTH) AF: 0.730 AC: 20866 AN: 28578

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

African (AFR) AF: 0.586 AC: 24316 AN: 41474

American (AMR) AF: 0.722 AC: 11057 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2651 AN: 3472

East Asian (EAS) AF: 0.654 AC: 3379 AN: 5170

South Asian (SAS) AF: 0.762 AC: 3666 AN: 4814

European-Finnish (FIN) AF: 0.704 AC: 7450 AN: 10582

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51224 AN: 67984

Other (OTH) AF: 0.717 AC: 1515 AN: 2112

Alfa AF: 0.722 Hom.: 6944

Bravo AF: 0.694

Asia WGS AF: 0.651 AC: 2262 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.68
PhyloP100		-0.30
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4638418; hg19: chr13-20978504;