NM_015974.3:c.847-123G>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015974.3(CRYL1):​c.847-123G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000388 in 514,802 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: CRYL1 NM_015974.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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>T		intron	N/A	NP_057058.2	Q9Y2S2-1
	CRYL1	NM_001363647.2		c.685-123G>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.847-123G>T		intron	N/A	ENSP00000298248.7	Q9Y2S2-1
	CRYL1	ENST00000382812.5	TSL:1	c.781-123G>T		intron	N/A	ENSP00000372262.1	Q9Y2S2-2
	CRYL1	ENST00000887623.1		c.808-123G>T		intron	N/A	ENSP00000557682.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000388 AC: 2 AN: 514802 Hom.: 0 AF XY: 0.00000735 AC XY: 2 AN XY: 271958

African (AFR) AF: 0.00 AC: 0 AN: 13982

American (AMR) AF: 0.00 AC: 0 AN: 23458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15238

East Asian (EAS) AF: 0.00 AC: 0 AN: 31696

South Asian (SAS) AF: 0.00 AC: 0 AN: 49232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31642

Middle Eastern (MID) AF: 0.000389 AC: 1 AN: 2570

European-Non Finnish (NFE) AF: 0.00000314 AC: 1 AN: 318382

Other (OTH) AF: 0.00 AC: 0 AN: 28602

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.8
DANN	Benign	0.71
PhyloP100		-0.30

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: rs4638418; hg19: chr13-20978504;